NAD(P)HX dehydratase (NAXD) deficiency due to a novel biallelic missense variant and review of literature
This study adds to the phenotypic and mutational spectrum of PEBEL2. We review the existing phenotypic and genotypic information for the individuals with this neurometabolic condition.PMID:34161859 | DOI:10.1016/j.ejmg.2021.104266 (Source: European Journal of Medical Genetics)
Source: European Journal of Medical Genetics - June 23, 2021 Category: Genetics & Stem Cells Authors: Purvi Majethia Shivani Mishra Lakshmi Priya Rao Raghavendra Rao Anju Shukla Source Type: research

Facial analysis technology for the detection of down syndrome in the Democratic Republic of the Congo
Eur J Med Genet. 2021 Jun 20:104267. doi: 10.1016/j.ejmg.2021.104267. Online ahead of print.ABSTRACTDown syndrome is one of the most common chromosomal anomalies affecting the world's population, with an estimated frequency of 1 in 700 live births. Despite its relatively high prevalence, diagnostic rates based on clinical features have remained under 70% for most of the developed world and even lower in countries with limited resources. While genetic and cytogenetic confirmation greatly increases the diagnostic rate, such resources are often non-existent in many low- and middle-income countries, particularly in Sub-Saharan...
Source: European Journal of Medical Genetics - June 23, 2021 Category: Genetics & Stem Cells Authors: Antonio R Porras Matthew S Bramble Kizito B A Mosema D'Andre Spencer C écile Dakande Hans Manya Neerja Vashist Esther Likuba Joachim Mukau Ebwel Celeste Musasa Helen Malherbe Bilal Mohammed Carlos Tor-Diez Dieudonn é Mumba Ngoyi Desire Tshala Katumbay M Source Type: research

Two novel variants in PLOD1 causing hydrocephalus in female newborn with kyphoscoliotic Ehlers-Danlos syndrome
Eur J Med Genet. 2021 Jun 20:104269. doi: 10.1016/j.ejmg.2021.104269. Online ahead of print.ABSTRACTThe kyphoscoliotic Ehlers-Danlos syndrome (kEDS) is a rare autosomal recessive connective tissue disorder characterized by hyperextensible skin and joints, kyphoscoliosis, and severe muscle hypotonia at birth. Causal variants have been identified in PLOD1 resulting in lysyl hydroxylase deficiency responsible for kEDS. However, the detailed phenotype of kEDS during the perinatal period is still poorly recognized. Here, we describe a case of a female newborn presenting with prenatal hydrocephalus and severe hypotonia after bir...
Source: European Journal of Medical Genetics - June 23, 2021 Category: Genetics & Stem Cells Authors: Yingchun Zhao Jingjing Sun Yihuan Chen Yong Hu Xiaohui Gong Li Ma Source Type: research

Further delineation of PIGB-related early infantile epileptic encephalopathy
We report on a 5 year-old girl born from consanguineous parents, manifesting severe global developmental delay with absent speech, mixed peripheral polyneuropathy, hypotonia, bilateral equino-varo-supinated-cavus foot, early-onset scoliosis, elevated serum alkaline phosphatase and a single episode of febrile status epilepticus. Hypomyelination was documented on brain MRI. Whole-exome sequencing (WES) disclosed the likely pathogenic biallelic PIGB NM_004855.4: c.463G> C, p.(Asp155His) missense variant. In our patient, while other characteristic clinical, neuroimaging and laboratory findings (as described in the first res...
Source: European Journal of Medical Genetics - June 23, 2021 Category: Genetics & Stem Cells Authors: Silvia Schiavoni Carlotta Spagnoli Susanna Rizzi Grazia Gabriella Salerno Daniele Frattini Patrizia Bergonzini Francesco Pisani Carlo Fusco Source Type: research

Monogenic lupus due to DNASE1L3 deficiency in a pediatric patient with urticarial rash, hypocomplementemia, pulmonary hemorrhage, and immune-complex glomerulonephritis
In conclusion, DNASE1L3 deficiency should be thought when juvenile SLE occurs with early disease-onset, pulmonary hemorrhage, glomerulonephritis, and recurrent urticarial rash along with ANCA positivity.PMID:34161863 | DOI:10.1016/j.ejmg.2021.104262 (Source: European Journal of Medical Genetics)
Source: European Journal of Medical Genetics - June 23, 2021 Category: Genetics & Stem Cells Authors: Rabia Miray Kisla Ekinci Sibel Balci Dilek Ozcan Bahriye Atmis Atil Bisgin Source Type: research

A case of digenic maturity onset diabetes of the young with heterozygous variants in both HNF1 Α and HNF1Β genes
CONCLUSION: Digenic inheritance of MODY pathogenic variants is probably more common than currently reported in literature. The use of Next Generation Sequencing panels in testing strategies for MODY could unmask such cases that would otherwise remain undiagnosed.PMID:34161864 | DOI:10.1016/j.ejmg.2021.104264 (Source: European Journal of Medical Genetics)
Source: European Journal of Medical Genetics - June 23, 2021 Category: Genetics & Stem Cells Authors: Konstantina Patouni Ondrej Cinek Stepanka Pruhova Lenka Elblova Maria Xatzipsalti Amalia Sertedaki Andriani Vazeou Source Type: research

Aberrant splicing and transcriptional activity of TPP1 result in CLN2-like disorder
We describe an individual with a presentation suggestive of an attenuated CLN2 phenotype, including a history of regression, recent-onset microcephaly and spasticity from age five years. Exome sequencing revealed two variants inherited in trans in TPP1, NM_000391.4:c.225A>G; p.(Gln75 = ) and NM_000391.4:c.1012C>G; p.(Gln338Glu), both classified as variants of uncertain significance. TPP1 activity was found to be significantly reduced in fibroblasts of the affected individual. RNAseq was performed to assess the impact of compound heterozygous variants in TPP1 and enabled the identification of three aberrant splicing e...
Source: European Journal of Medical Genetics - June 14, 2021 Category: Genetics & Stem Cells Authors: Guy Helman Lauren E Taylor Marzena Walkiewicz Maelle Le Moing Stefanie Eggers Joy Yaplito-Lee Maria Fuller Gabriel Dabscheck Victoria Rodriguez-Casero Susan M White Cas Simons Source Type: research

Aberrant splicing and transcriptional activity of TPP1 result in CLN2-like disorder
We describe an individual with a presentation suggestive of an attenuated CLN2 phenotype, including a history of regression, recent-onset microcephaly and spasticity from age five years. Exome sequencing revealed two variants inherited in trans in TPP1, NM_000391.4:c.225A>G; p.(Gln75 = ) and NM_000391.4:c.1012C>G; p.(Gln338Glu), both classified as variants of uncertain significance. TPP1 activity was found to be significantly reduced in fibroblasts of the affected individual. RNAseq was performed to assess the impact of compound heterozygous variants in TPP1 and enabled the identification of three aberrant splicing e...
Source: European Journal of Medical Genetics - June 14, 2021 Category: Genetics & Stem Cells Authors: Guy Helman Lauren E Taylor Marzena Walkiewicz Maelle Le Moing Stefanie Eggers Joy Yaplito-Lee Maria Fuller Gabriel Dabscheck Victoria Rodriguez-Casero Susan M White Cas Simons Source Type: research

Aberrant splicing and transcriptional activity of TPP1 result in CLN2-like disorder
We describe an individual with a presentation suggestive of an attenuated CLN2 phenotype, including a history of regression, recent-onset microcephaly and spasticity from age five years. Exome sequencing revealed two variants inherited in trans in TPP1, NM_000391.4:c.225A>G; p.(Gln75 = ) and NM_000391.4:c.1012C>G; p.(Gln338Glu), both classified as variants of uncertain significance. TPP1 activity was found to be significantly reduced in fibroblasts of the affected individual. RNAseq was performed to assess the impact of compound heterozygous variants in TPP1 and enabled the identification of three aberrant splicing e...
Source: European Journal of Medical Genetics - June 14, 2021 Category: Genetics & Stem Cells Authors: Guy Helman Lauren E Taylor Marzena Walkiewicz Maelle Le Moing Stefanie Eggers Joy Yaplito-Lee Maria Fuller Gabriel Dabscheck Victoria Rodriguez-Casero Susan M White Cas Simons Source Type: research

Aberrant splicing and transcriptional activity of TPP1 result in CLN2-like disorder
We describe an individual with a presentation suggestive of an attenuated CLN2 phenotype, including a history of regression, recent-onset microcephaly and spasticity from age five years. Exome sequencing revealed two variants inherited in trans in TPP1, NM_000391.4:c.225A>G; p.(Gln75 = ) and NM_000391.4:c.1012C>G; p.(Gln338Glu), both classified as variants of uncertain significance. TPP1 activity was found to be significantly reduced in fibroblasts of the affected individual. RNAseq was performed to assess the impact of compound heterozygous variants in TPP1 and enabled the identification of three aberrant splicing e...
Source: European Journal of Medical Genetics - June 14, 2021 Category: Genetics & Stem Cells Authors: Guy Helman Lauren E Taylor Marzena Walkiewicz Maelle Le Moing Stefanie Eggers Joy Yaplito-Lee Maria Fuller Gabriel Dabscheck Victoria Rodriguez-Casero Susan M White Cas Simons Source Type: research

Aberrant splicing and transcriptional activity of TPP1 result in CLN2-like disorder
We describe an individual with a presentation suggestive of an attenuated CLN2 phenotype, including a history of regression, recent-onset microcephaly and spasticity from age five years. Exome sequencing revealed two variants inherited in trans in TPP1, NM_000391.4:c.225A>G; p.(Gln75 = ) and NM_000391.4:c.1012C>G; p.(Gln338Glu), both classified as variants of uncertain significance. TPP1 activity was found to be significantly reduced in fibroblasts of the affected individual. RNAseq was performed to assess the impact of compound heterozygous variants in TPP1 and enabled the identification of three aberrant splicing e...
Source: European Journal of Medical Genetics - June 14, 2021 Category: Genetics & Stem Cells Authors: Guy Helman Lauren E Taylor Marzena Walkiewicz Maelle Le Moing Stefanie Eggers Joy Yaplito-Lee Maria Fuller Gabriel Dabscheck Victoria Rodriguez-Casero Susan M White Cas Simons Source Type: research

Aberrant splicing and transcriptional activity of TPP1 result in CLN2-like disorder
We describe an individual with a presentation suggestive of an attenuated CLN2 phenotype, including a history of regression, recent-onset microcephaly and spasticity from age five years. Exome sequencing revealed two variants inherited in trans in TPP1, NM_000391.4:c.225A>G; p.(Gln75 = ) and NM_000391.4:c.1012C>G; p.(Gln338Glu), both classified as variants of uncertain significance. TPP1 activity was found to be significantly reduced in fibroblasts of the affected individual. RNAseq was performed to assess the impact of compound heterozygous variants in TPP1 and enabled the identification of three aberrant splicing e...
Source: European Journal of Medical Genetics - June 14, 2021 Category: Genetics & Stem Cells Authors: Guy Helman Lauren E Taylor Marzena Walkiewicz Maelle Le Moing Stefanie Eggers Joy Yaplito-Lee Maria Fuller Gabriel Dabscheck Victoria Rodriguez-Casero Susan M White Cas Simons Source Type: research

Aberrant splicing and transcriptional activity of TPP1 result in CLN2-like disorder
We describe an individual with a presentation suggestive of an attenuated CLN2 phenotype, including a history of regression, recent-onset microcephaly and spasticity from age five years. Exome sequencing revealed two variants inherited in trans in TPP1, NM_000391.4:c.225A>G; p.(Gln75 = ) and NM_000391.4:c.1012C>G; p.(Gln338Glu), both classified as variants of uncertain significance. TPP1 activity was found to be significantly reduced in fibroblasts of the affected individual. RNAseq was performed to assess the impact of compound heterozygous variants in TPP1 and enabled the identification of three aberrant splicing e...
Source: European Journal of Medical Genetics - June 14, 2021 Category: Genetics & Stem Cells Authors: Guy Helman Lauren E Taylor Marzena Walkiewicz Maelle Le Moing Stefanie Eggers Joy Yaplito-Lee Maria Fuller Gabriel Dabscheck Victoria Rodriguez-Casero Susan M White Cas Simons Source Type: research

A patient with POLA1 splice variant expands the yet evolving phenotype of Van Esch O'Driscoll syndrome
We report a three-year-old child with VEODS having borderline intellectual disability due to a novel splice site variant causing exon 6 skipping and reduced POLA1 expression.PMID:34119699 | DOI:10.1016/j.ejmg.2021.104261 (Source: European Journal of Medical Genetics)
Source: European Journal of Medical Genetics - June 13, 2021 Category: Genetics & Stem Cells Authors: Mounika Endrakanti Sumedha Saluja Abdul S Ethayathulla Savita Sapra Ashwin Dalal Jayanth Kumar Palanichamy Neerja Gupta Source Type: research

A patient with POLA1 splice variant expands the yet evolving phenotype of Van Esch O'Driscoll syndrome
We report a three-year-old child with VEODS having borderline intellectual disability due to a novel splice site variant causing exon 6 skipping and reduced POLA1 expression.PMID:34119699 | DOI:10.1016/j.ejmg.2021.104261 (Source: European Journal of Medical Genetics)
Source: European Journal of Medical Genetics - June 13, 2021 Category: Genetics & Stem Cells Authors: Mounika Endrakanti Sumedha Saluja Abdul S Ethayathulla Savita Sapra Ashwin Dalal Jayanth Kumar Palanichamy Neerja Gupta Source Type: research

A homozygous nonsense mutation early in exon 5 of BRCA2 is associated with very severe Fanconi anemia
Eur J Med Genet. 2021 Jun 9:104260. doi: 10.1016/j.ejmg.2021.104260. Online ahead of print.ABSTRACTFanconi anemia (FA) due to biallelic mutations in the BRCA2 gene is very rare and associated with an extremely high risk of early-onset of aggressive childhood malignancies, predominantly brain tumors, leukemia, and nephroblastoma. Here, we present a consanguineous family with three affected children of the D1 subtype of FA and describe the clinical consequences of the earliest known biallelic nonsense/stop-gain germ-line mutation in BRCA2, exon 5 c.469A>T, that leads to a premature stop of translation, p.Lys157*. The thre...
Source: European Journal of Medical Genetics - June 12, 2021 Category: Genetics & Stem Cells Authors: Ivana Radulovic Alma Kuechler Michael M Sch ündeln Michael Paulussen Nils von Neuhoff Dirk Reinhardt Helmut Hanenberg Source Type: research

A unique case of progressive hemifacial microsomia or Parry-Romberg syndrome associated with limb and brain anomalies with normal neurological findings: A review of the literature
This report brings attention to the complicated relationship between facial, limb and brain imaging findings in Parry-Romberg syndrome and differentiates it from hemifacial microsomia syndrome.PMID:34082156 | DOI:10.1016/j.ejmg.2021.104234 (Source: European Journal of Medical Genetics)
Source: European Journal of Medical Genetics - June 3, 2021 Category: Genetics & Stem Cells Authors: Anandita Pattnaik Alexandra Lim Sara Sabeti Ashley Kwon Katherine Hall Ira Lott Virginia Kimonis Source Type: research

A unique case of progressive hemifacial microsomia or Parry-Romberg syndrome associated with limb and brain anomalies with normal neurological findings: A review of the literature
This report brings attention to the complicated relationship between facial, limb and brain imaging findings in Parry-Romberg syndrome and differentiates it from hemifacial microsomia syndrome.PMID:34082156 | DOI:10.1016/j.ejmg.2021.104234 (Source: European Journal of Medical Genetics)
Source: European Journal of Medical Genetics - June 3, 2021 Category: Genetics & Stem Cells Authors: Anandita Pattnaik Alexandra Lim Sara Sabeti Ashley Kwon Katherine Hall Ira Lott Virginia Kimonis Source Type: research

A unique case of progressive hemifacial microsomia or Parry-Romberg syndrome associated with limb and brain anomalies with normal neurological findings: A review of the literature
This report brings attention to the complicated relationship between facial, limb and brain imaging findings in Parry-Romberg syndrome and differentiates it from hemifacial microsomia syndrome.PMID:34082156 | DOI:10.1016/j.ejmg.2021.104234 (Source: European Journal of Medical Genetics)
Source: European Journal of Medical Genetics - June 3, 2021 Category: Genetics & Stem Cells Authors: Anandita Pattnaik Alexandra Lim Sara Sabeti Ashley Kwon Katherine Hall Ira Lott Virginia Kimonis Source Type: research

A unique case of progressive hemifacial microsomia or Parry-Romberg syndrome associated with limb and brain anomalies with normal neurological findings: A review of the literature
This report brings attention to the complicated relationship between facial, limb and brain imaging findings in Parry-Romberg syndrome and differentiates it from hemifacial microsomia syndrome.PMID:34082156 | DOI:10.1016/j.ejmg.2021.104234 (Source: European Journal of Medical Genetics)
Source: European Journal of Medical Genetics - June 3, 2021 Category: Genetics & Stem Cells Authors: Anandita Pattnaik Alexandra Lim Sara Sabeti Ashley Kwon Katherine Hall Ira Lott Virginia Kimonis Source Type: research

A unique case of progressive hemifacial microsomia or Parry-Romberg syndrome associated with limb and brain anomalies with normal neurological findings: A review of the literature
This report brings attention to the complicated relationship between facial, limb and brain imaging findings in Parry-Romberg syndrome and differentiates it from hemifacial microsomia syndrome.PMID:34082156 | DOI:10.1016/j.ejmg.2021.104234 (Source: European Journal of Medical Genetics)
Source: European Journal of Medical Genetics - June 3, 2021 Category: Genetics & Stem Cells Authors: Anandita Pattnaik Alexandra Lim Sara Sabeti Ashley Kwon Katherine Hall Ira Lott Virginia Kimonis Source Type: research

A unique case of progressive hemifacial microsomia or Parry-Romberg syndrome associated with limb and brain anomalies with normal neurological findings: A review of the literature
This report brings attention to the complicated relationship between facial, limb and brain imaging findings in Parry-Romberg syndrome and differentiates it from hemifacial microsomia syndrome.PMID:34082156 | DOI:10.1016/j.ejmg.2021.104234 (Source: European Journal of Medical Genetics)
Source: European Journal of Medical Genetics - June 3, 2021 Category: Genetics & Stem Cells Authors: Anandita Pattnaik Alexandra Lim Sara Sabeti Ashley Kwon Katherine Hall Ira Lott Virginia Kimonis Source Type: research

A unique case of progressive hemifacial microsomia or Parry-Romberg syndrome associated with limb and brain anomalies with normal neurological findings: A review of the literature
This report brings attention to the complicated relationship between facial, limb and brain imaging findings in Parry-Romberg syndrome and differentiates it from hemifacial microsomia syndrome.PMID:34082156 | DOI:10.1016/j.ejmg.2021.104234 (Source: European Journal of Medical Genetics)
Source: European Journal of Medical Genetics - June 3, 2021 Category: Genetics & Stem Cells Authors: Anandita Pattnaik Alexandra Lim Sara Sabeti Ashley Kwon Katherine Hall Ira Lott Virginia Kimonis Source Type: research

A unique case of progressive hemifacial microsomia or Parry-Romberg syndrome associated with limb and brain anomalies with normal neurological findings: A review of the literature
This report brings attention to the complicated relationship between facial, limb and brain imaging findings in Parry-Romberg syndrome and differentiates it from hemifacial microsomia syndrome.PMID:34082156 | DOI:10.1016/j.ejmg.2021.104234 (Source: European Journal of Medical Genetics)
Source: European Journal of Medical Genetics - June 3, 2021 Category: Genetics & Stem Cells Authors: Anandita Pattnaik Alexandra Lim Sara Sabeti Ashley Kwon Katherine Hall Ira Lott Virginia Kimonis Source Type: research

A case of ATR-X syndrome with mitochondrial respiratory chain dysfunction
Eur J Med Genet. 2021 May 26:104251. doi: 10.1016/j.ejmg.2021.104251. Online ahead of print.ABSTRACTAlpha-thalassemia X-linked intellectual disability (ATR-X) syndrome is caused by a mutation in ATRX, which is essential for proper chromatin remodeling. ATRX dysfunction leads to dysregulation of many genes due to abnormal chromatin remodeling, and causes a multisystem disorder in patients with ATR-X. Because mitochondrial disorders also show multisystem involvement, whether mitochondrial function is affected in patients with ATR-X is of interest. Here, we report a case of a 4-year-old male with a mutation (NM_000489.4: c.73...
Source: European Journal of Medical Genetics - May 29, 2021 Category: Genetics & Stem Cells Authors: Clinical Reports Kaori Aiba Yuji Nakamura Mari Sugimoto Yukiko Yatsuka Yasushi Okazaki Kei Murayama Akira Ohtake Kenji Yokochi Shinji Saitoh Source Type: research

Expanding the spectrum of endocrinopathies identified in Schaaf-Yang syndrome - a case report and review of the literature
We describe a unique case of an infant with Schaaf-Yang syndrome that presented with persistent hyperinsulinism unresponsive to diazoxide. Furthermore, we conducted a literature review of the endocrine abnormalities described in MAGEL2 related disorders. The case presented expands the clinical phenotype of Schaaf-Yang syndrome and emphasizes the importance of endocrine follow-up in these patients. Further investigation into the role of MAGEL2 in the regulation of pancreatic beta-cell insulin secretion, will improve our understanding of the abnormalities in glucose regulation in this syndrome.PMID:34051361 | DOI:10.1016/j.e...
Source: European Journal of Medical Genetics - May 29, 2021 Category: Genetics & Stem Cells Authors: Rana Halloun Clair Habib Nina Ekhilevitch Ram Weiss Dov Tiosano Michal Cohen Source Type: research

A case of ATR-X syndrome with mitochondrial respiratory chain dysfunction
Eur J Med Genet. 2021 May 26:104251. doi: 10.1016/j.ejmg.2021.104251. Online ahead of print.ABSTRACTAlpha-thalassemia X-linked intellectual disability (ATR-X) syndrome is caused by a mutation in ATRX, which is essential for proper chromatin remodeling. ATRX dysfunction leads to dysregulation of many genes due to abnormal chromatin remodeling, and causes a multisystem disorder in patients with ATR-X. Because mitochondrial disorders also show multisystem involvement, whether mitochondrial function is affected in patients with ATR-X is of interest. Here, we report a case of a 4-year-old male with a mutation (NM_000489.4: c.73...
Source: European Journal of Medical Genetics - May 29, 2021 Category: Genetics & Stem Cells Authors: Clinical Reports Kaori Aiba Yuji Nakamura Mari Sugimoto Yukiko Yatsuka Yasushi Okazaki Kei Murayama Akira Ohtake Kenji Yokochi Shinji Saitoh Source Type: research

Expanding the spectrum of endocrinopathies identified in Schaaf-Yang syndrome - a case report and review of the literature
We describe a unique case of an infant with Schaaf-Yang syndrome that presented with persistent hyperinsulinism unresponsive to diazoxide. Furthermore, we conducted a literature review of the endocrine abnormalities described in MAGEL2 related disorders. The case presented expands the clinical phenotype of Schaaf-Yang syndrome and emphasizes the importance of endocrine follow-up in these patients. Further investigation into the role of MAGEL2 in the regulation of pancreatic beta-cell insulin secretion, will improve our understanding of the abnormalities in glucose regulation in this syndrome.PMID:34051361 | DOI:10.1016/j.e...
Source: European Journal of Medical Genetics - May 29, 2021 Category: Genetics & Stem Cells Authors: Rana Halloun Clair Habib Nina Ekhilevitch Ram Weiss Dov Tiosano Michal Cohen Source Type: research

A case of ATR-X syndrome with mitochondrial respiratory chain dysfunction
Eur J Med Genet. 2021 May 26:104251. doi: 10.1016/j.ejmg.2021.104251. Online ahead of print.ABSTRACTAlpha-thalassemia X-linked intellectual disability (ATR-X) syndrome is caused by a mutation in ATRX, which is essential for proper chromatin remodeling. ATRX dysfunction leads to dysregulation of many genes due to abnormal chromatin remodeling, and causes a multisystem disorder in patients with ATR-X. Because mitochondrial disorders also show multisystem involvement, whether mitochondrial function is affected in patients with ATR-X is of interest. Here, we report a case of a 4-year-old male with a mutation (NM_000489.4: c.73...
Source: European Journal of Medical Genetics - May 29, 2021 Category: Genetics & Stem Cells Authors: Clinical Reports Kaori Aiba Yuji Nakamura Mari Sugimoto Yukiko Yatsuka Yasushi Okazaki Kei Murayama Akira Ohtake Kenji Yokochi Shinji Saitoh Source Type: research

Expanding the spectrum of endocrinopathies identified in Schaaf-Yang syndrome - a case report and review of the literature
We describe a unique case of an infant with Schaaf-Yang syndrome that presented with persistent hyperinsulinism unresponsive to diazoxide. Furthermore, we conducted a literature review of the endocrine abnormalities described in MAGEL2 related disorders. The case presented expands the clinical phenotype of Schaaf-Yang syndrome and emphasizes the importance of endocrine follow-up in these patients. Further investigation into the role of MAGEL2 in the regulation of pancreatic beta-cell insulin secretion, will improve our understanding of the abnormalities in glucose regulation in this syndrome.PMID:34051361 | DOI:10.1016/j.e...
Source: European Journal of Medical Genetics - May 29, 2021 Category: Genetics & Stem Cells Authors: Rana Halloun Clair Habib Nina Ekhilevitch Ram Weiss Dov Tiosano Michal Cohen Source Type: research

A case of ATR-X syndrome with mitochondrial respiratory chain dysfunction
Eur J Med Genet. 2021 May 26:104251. doi: 10.1016/j.ejmg.2021.104251. Online ahead of print.ABSTRACTAlpha-thalassemia X-linked intellectual disability (ATR-X) syndrome is caused by a mutation in ATRX, which is essential for proper chromatin remodeling. ATRX dysfunction leads to dysregulation of many genes due to abnormal chromatin remodeling, and causes a multisystem disorder in patients with ATR-X. Because mitochondrial disorders also show multisystem involvement, whether mitochondrial function is affected in patients with ATR-X is of interest. Here, we report a case of a 4-year-old male with a mutation (NM_000489.4: c.73...
Source: European Journal of Medical Genetics - May 29, 2021 Category: Genetics & Stem Cells Authors: Clinical Reports Kaori Aiba Yuji Nakamura Mari Sugimoto Yukiko Yatsuka Yasushi Okazaki Kei Murayama Akira Ohtake Kenji Yokochi Shinji Saitoh Source Type: research

Expanding the spectrum of endocrinopathies identified in Schaaf-Yang syndrome - a case report and review of the literature
We describe a unique case of an infant with Schaaf-Yang syndrome that presented with persistent hyperinsulinism unresponsive to diazoxide. Furthermore, we conducted a literature review of the endocrine abnormalities described in MAGEL2 related disorders. The case presented expands the clinical phenotype of Schaaf-Yang syndrome and emphasizes the importance of endocrine follow-up in these patients. Further investigation into the role of MAGEL2 in the regulation of pancreatic beta-cell insulin secretion, will improve our understanding of the abnormalities in glucose regulation in this syndrome.PMID:34051361 | DOI:10.1016/j.e...
Source: European Journal of Medical Genetics - May 29, 2021 Category: Genetics & Stem Cells Authors: Rana Halloun Clair Habib Nina Ekhilevitch Ram Weiss Dov Tiosano Michal Cohen Source Type: research

Concomitant congenital CMV infection and inherited liver diseases
We report a series of three patients, diagnosed with hereditary liver diseases: progressive familial intrahepatic cholestasis (PFIC) type IV, alpha 1 anti-trypsin deficiency (A1ATD) and Alagille syndrome (ALGS), who were also diagnosed with cCMV infection. All patients were treated with valgancilovir for symptomatic cCMV infection (6-12 months), followed by suppressive dosing in the 2 patients with PFIC and A1ATD. Following 15-24 months of follow-up - the patients with PFIC and A1ATD developed severe liver failure, and the third had ongoing cholestatic disease with stable synthetic function. We propose a significant contri...
Source: European Journal of Medical Genetics - May 23, 2021 Category: Genetics & Stem Cells Authors: Rana Swed-Tobia Imad Kassis Karin Weiss Galit Tal Ron Shaoul Tzipora C Falik-Zaccai Hanna Mandel Michal Meir Source Type: research

Concomitant Congenital CMV Infection and Inherited Liver Diseases
We report a series of three patients, diagnosed with hereditary liver diseases: progressive familial intrahepatic cholestasis (PFIC) type IV, alpha 1 anti-trypsin deficiency (A1ATD) and Alagille syndrome (ALGS), who were also diagnosed with cCMV infection. All patients were treated with valgancilovir for symptomatic cCMV infection (6-12 months), followed by suppressive dosing in the 2 patients with PFIC and A1ATD. Following 15-24 months of follow-up - the patients with PFIC and A1ATD developed severe liver failure, and the third had ongoing cholestatic disease with stable synthetic function. We propose a significant contri...
Source: European Journal of Medical Genetics - May 23, 2021 Category: Genetics & Stem Cells Authors: Rana Swed-Tobia Imad Kassis Karin Weiss Galit Tal Ron Shaoul Tzipora C Falik-Zaccai Hanna Mandel Michal Meir Source Type: research

Concomitant Congenital CMV Infection and Inherited Liver Diseases
We report a series of three patients, diagnosed with hereditary liver diseases: progressive familial intrahepatic cholestasis (PFIC) type IV, alpha 1 anti-trypsin deficiency (A1ATD) and Alagille syndrome (ALGS), who were also diagnosed with cCMV infection. All patients were treated with valgancilovir for symptomatic cCMV infection (6-12 months), followed by suppressive dosing in the 2 patients with PFIC and A1ATD. Following 15-24 months of follow-up - the patients with PFIC and A1ATD developed severe liver failure, and the third had ongoing cholestatic disease with stable synthetic function. We propose a significant contri...
Source: European Journal of Medical Genetics - May 23, 2021 Category: Genetics & Stem Cells Authors: Rana Swed-Tobia Imad Kassis Karin Weiss Galit Tal Ron Shaoul Tzipora C Falik-Zaccai Hanna Mandel Michal Meir Source Type: research

Concomitant Congenital CMV Infection and Inherited Liver Diseases
We report a series of three patients, diagnosed with hereditary liver diseases: progressive familial intrahepatic cholestasis (PFIC) type IV, alpha 1 anti-trypsin deficiency (A1ATD) and Alagille syndrome (ALGS), who were also diagnosed with cCMV infection. All patients were treated with valgancilovir for symptomatic cCMV infection (6-12 months), followed by suppressive dosing in the 2 patients with PFIC and A1ATD. Following 15-24 months of follow-up - the patients with PFIC and A1ATD developed severe liver failure, and the third had ongoing cholestatic disease with stable synthetic function. We propose a significant contri...
Source: European Journal of Medical Genetics - May 23, 2021 Category: Genetics & Stem Cells Authors: Rana Swed-Tobia Imad Kassis Karin Weiss Galit Tal Ron Shaoul Tzipora C Falik-Zaccai Hanna Mandel Michal Meir Source Type: research

Concomitant Congenital CMV Infection and Inherited Liver Diseases
We report a series of three patients, diagnosed with hereditary liver diseases: progressive familial intrahepatic cholestasis (PFIC) type IV, alpha 1 anti-trypsin deficiency (A1ATD) and Alagille syndrome (ALGS), who were also diagnosed with cCMV infection. All patients were treated with valgancilovir for symptomatic cCMV infection (6-12 months), followed by suppressive dosing in the 2 patients with PFIC and A1ATD. Following 15-24 months of follow-up - the patients with PFIC and A1ATD developed severe liver failure, and the third had ongoing cholestatic disease with stable synthetic function. We propose a significant contri...
Source: European Journal of Medical Genetics - May 23, 2021 Category: Genetics & Stem Cells Authors: Rana Swed-Tobia Imad Kassis Karin Weiss Galit Tal Ron Shaoul Tzipora C Falik-Zaccai Hanna Mandel Michal Meir Source Type: research

Spontaneous rescue of a FMR1 repeat expansion and review of deletions in the FMR1 non-coding region
We report a deletion in the 5' UTR of FMR1 in an unaffected male infant and review 12 reported deletions involving only the non-coding region of FMR1 .Genetic testing was requested in a male infant born to a mother harbouring a FMR1 full mutation. The maternal grandmother carried a FMR1 premutation.FMR1 CGG repeats were analysed using repeat-primed PCR. Only a short PCR fragment was amplified and subsequent Sanger sequencing detected an 88 bp deletion in hemizygous form. The deletion included all CGG repeats and flanking sequences but noFMR1 exons. Linkage analysis using STR markers revealed that the deletion had occurred ...
Source: European Journal of Medical Genetics - May 22, 2021 Category: Genetics & Stem Cells Authors: Emilie Erbs Jesper Fenger-Gr øn Cecilie Mondrup Jacobsen Dorte Launholt Lildballe Maria Rasmussen Source Type: research

Phenotype of ST3GAL3 Deficient Patients: a Case and Review of the Literature
Eur J Med Genet. 2021 May 19:104250. doi: 10.1016/j.ejmg.2021.104250. Online ahead of print.ABSTRACTST3GAL3 deficiency is an extremely rare autosomal recessive disorder caused by pathogenic mutations in the ST3GAL3 gene. Epilepsy, motor development delay, severe intellectual disability, and behavioral disorders have been reported to be associated with ST3GAL3 deficiency. In the present study, ST3GAL3 deficiency was caused by a homozygous splice-site mutation (NM_174964.4: c.936+1delG) in ST3GAL3. The patient described in this study was clinically similar to previously reported cases; nevertheless, we were able to detect re...
Source: European Journal of Medical Genetics - May 22, 2021 Category: Genetics & Stem Cells Authors: Hossein Jafari Khamirani Sina Zoghi Fatemeh Faghihi Seyed Alireza Dastgheib Hamidreza Hassanipour Seyed Mohammad Bagher Tabei Sanaz Mohammadi Marjan Masoudi Shiva Poorang Elham Ehsani Mehdi Dianatpour Source Type: research

Spontaneous rescue of a FMR1 repeat expansion and review of deletions in the FMR1 non-coding region
We report a deletion in the 5' UTR of FMR1 in an unaffected male infant and review 12 reported deletions involving only the non-coding region of FMR1 .Genetic testing was requested in a male infant born to a mother harbouring a FMR1 full mutation. The maternal grandmother carried a FMR1 premutation.FMR1 CGG repeats were analysed using repeat-primed PCR. Only a short PCR fragment was amplified and subsequent Sanger sequencing detected an 88 bp deletion in hemizygous form. The deletion included all CGG repeats and flanking sequences but noFMR1 exons. Linkage analysis using STR markers revealed that the deletion had occurred ...
Source: European Journal of Medical Genetics - May 22, 2021 Category: Genetics & Stem Cells Authors: Emilie Erbs Jesper Fenger-Gr øn Cecilie Mondrup Jacobsen Dorte Launholt Lildballe Maria Rasmussen Source Type: research

Phenotype of ST3GAL3 Deficient Patients: a Case and Review of the Literature
Eur J Med Genet. 2021 May 19:104250. doi: 10.1016/j.ejmg.2021.104250. Online ahead of print.ABSTRACTST3GAL3 deficiency is an extremely rare autosomal recessive disorder caused by pathogenic mutations in the ST3GAL3 gene. Epilepsy, motor development delay, severe intellectual disability, and behavioral disorders have been reported to be associated with ST3GAL3 deficiency. In the present study, ST3GAL3 deficiency was caused by a homozygous splice-site mutation (NM_174964.4: c.936+1delG) in ST3GAL3. The patient described in this study was clinically similar to previously reported cases; nevertheless, we were able to detect re...
Source: European Journal of Medical Genetics - May 22, 2021 Category: Genetics & Stem Cells Authors: Hossein Jafari Khamirani Sina Zoghi Fatemeh Faghihi Seyed Alireza Dastgheib Hamidreza Hassanipour Seyed Mohammad Bagher Tabei Sanaz Mohammadi Marjan Masoudi Shiva Poorang Elham Ehsani Mehdi Dianatpour Source Type: research

"Expansion of the CCDC22 associated Ritscher-Schinzel/3C syndrome and review of the literature: Should the minimal diagnostic criteria be revised?"
Eur J Med Genet. 2021 May 18:104246. doi: 10.1016/j.ejmg.2021.104246. Online ahead of print.ABSTRACTThe Ritscher-Schinzel syndrome (RTSCS) is a rare condition with craniofacial, cardiac and fossa posterior abnormalities. RTSCS is subdivided into Ritscher-Schinzel syndrome 1 (RTSCS1) caused by pathogenic variants in coiled-coil domain-containing protein 22 (CCDC22), and Ritscher-Schinzel syndrome 2 (RTSCS2) caused by pathogenic variants in WASH complex subunit 5 (WASHC5). CCDC22 is inherited in an X-linked recessive manner while WASHC5 is inherited in an autosomal recessive manner. Only 17 individuals with a molecular diagn...
Source: European Journal of Medical Genetics - May 21, 2021 Category: Genetics & Stem Cells Authors: Cathrine E Gjerulfsen Rikke S M øller Christina D Fenger Trine B Hammer Allan Bayat Source Type: research

"Expansion of the CCDC22 associated Ritscher-Schinzel/3C syndrome and review of the literature: Should the minimal diagnostic criteria be revised?"
Eur J Med Genet. 2021 May 18:104246. doi: 10.1016/j.ejmg.2021.104246. Online ahead of print.ABSTRACTThe Ritscher-Schinzel syndrome (RTSCS) is a rare condition with craniofacial, cardiac and fossa posterior abnormalities. RTSCS is subdivided into Ritscher-Schinzel syndrome 1 (RTSCS1) caused by pathogenic variants in coiled-coil domain-containing protein 22 (CCDC22), and Ritscher-Schinzel syndrome 2 (RTSCS2) caused by pathogenic variants in WASH complex subunit 5 (WASHC5). CCDC22 is inherited in an X-linked recessive manner while WASHC5 is inherited in an autosomal recessive manner. Only 17 individuals with a molecular diagn...
Source: European Journal of Medical Genetics - May 21, 2021 Category: Genetics & Stem Cells Authors: Cathrine E Gjerulfsen Rikke S M øller Christina D Fenger Trine B Hammer Allan Bayat Source Type: research

Seven patients with Smith-McCort Dysplasia 2: Four novel nonsense variants in RAB33B and follow-up findings
This study provides important data on long-term skeletal findings of the patients with SMC2.PMID:34000439 | DOI:10.1016/j.ejmg.2021.104248 (Source: European Journal of Medical Genetics)
Source: European Journal of Medical Genetics - May 17, 2021 Category: Genetics & Stem Cells Authors: Beyhan T üysüz Filiz Geyik Timur Y ıldırım Dilek Uluda ğ Alkaya Sabine Sharifova Ali Kafadar Source Type: research

Utility of clinical exome sequencing in the evaluation of neonates with suspected genetic condition - An observational study from tertiary neonatal care unit in South India
CONCLUSION: CES has a definite role in evaluation of suspected genetic conditions for diagnosis and prognostication . It also helps scientific society to build in additional evidence so that the "VUS" could be asserted as "likely pathogenic" . Our experience reiterates the importance of storing and archiving DNA of the affected child.PMID:34000440 | DOI:10.1016/j.ejmg.2021.104247 (Source: European Journal of Medical Genetics)
Source: European Journal of Medical Genetics - May 17, 2021 Category: Genetics & Stem Cells Authors: Dr R UshaDevi Dr Thinesh Kumar Dr Shaik Mohammad Shafi Jan Dr Ashok Chandrasekaran Dr Prakash Amboiram Dr Teena Koshy Dr Uma Maheswari B Source Type: research

Seven patients with Smith-McCort Dysplasia 2: Four novel nonsense variants in RAB33B and follow-up findings
This study provides important data on long-term skeletal findings of the patients with SMC2.PMID:34000439 | DOI:10.1016/j.ejmg.2021.104248 (Source: European Journal of Medical Genetics)
Source: European Journal of Medical Genetics - May 17, 2021 Category: Genetics & Stem Cells Authors: Beyhan T üysüz Filiz Geyik Timur Y ıldırım Dilek Uluda ğ Alkaya Sabine Sharifova Ali Kafadar Source Type: research

Utility of clinical exome sequencing in the evaluation of neonates with suspected genetic condition - An observational study from tertiary neonatal care unit in South India
CONCLUSION: CES has a definite role in evaluation of suspected genetic conditions for diagnosis and prognostication . It also helps scientific society to build in additional evidence so that the "VUS" could be asserted as "likely pathogenic" . Our experience reiterates the importance of storing and archiving DNA of the affected child.PMID:34000440 | DOI:10.1016/j.ejmg.2021.104247 (Source: European Journal of Medical Genetics)
Source: European Journal of Medical Genetics - May 17, 2021 Category: Genetics & Stem Cells Authors: Dr R UshaDevi Dr Thinesh Kumar Dr Shaik Mohammad Shafi Jan Dr Ashok Chandrasekaran Dr Prakash Amboiram Dr Teena Koshy Dr Uma Maheswari B Source Type: research

Seven patients with Smith-McCort Dysplasia 2: Four novel nonsense variants in RAB33B and follow-up findings
This study provides important data on long-term skeletal findings of the patients with SMC2.PMID:34000439 | DOI:10.1016/j.ejmg.2021.104248 (Source: European Journal of Medical Genetics)
Source: European Journal of Medical Genetics - May 17, 2021 Category: Genetics & Stem Cells Authors: Beyhan T üysüz Filiz Geyik Timur Y ıldırım Dilek Uluda ğ Alkaya Sabine Sharifova Ali Kafadar Source Type: research

Utility of clinical exome sequencing in the evaluation of neonates with suspected genetic condition - An observational study from tertiary neonatal care unit in South India
CONCLUSION: CES has a definite role in evaluation of suspected genetic conditions for diagnosis and prognostication . It also helps scientific society to build in additional evidence so that the "VUS" could be asserted as "likely pathogenic" . Our experience reiterates the importance of storing and archiving DNA of the affected child.PMID:34000440 | DOI:10.1016/j.ejmg.2021.104247 (Source: European Journal of Medical Genetics)
Source: European Journal of Medical Genetics - May 17, 2021 Category: Genetics & Stem Cells Authors: Dr R UshaDevi Dr Thinesh Kumar Dr Shaik Mohammad Shafi Jan Dr Ashok Chandrasekaran Dr Prakash Amboiram Dr Teena Koshy Dr Uma Maheswari B Source Type: research

Seven patients with Smith-McCort Dysplasia 2: Four novel nonsense variants in RAB33B and follow-up findings
This study provides important data on long-term skeletal findings of the patients with SMC2.PMID:34000439 | DOI:10.1016/j.ejmg.2021.104248 (Source: European Journal of Medical Genetics)
Source: European Journal of Medical Genetics - May 17, 2021 Category: Genetics & Stem Cells Authors: Beyhan T üysüz Filiz Geyik Timur Y ıldırım Dilek Uluda ğ Alkaya Sabine Sharifova Ali Kafadar Source Type: research