A Recurrent Variant in < b > < i > MAGEL2 < /i > < /b > in Five Siblings with Severe Respiratory Disturbance after Birth
We report 5 newborns affected with SHFYNG in one family. Trio exome analysis revealed a heterozygous c.1996dupC frameshift mutation inMAGEL2 inherited from the unaffected father. The phenotypes showed strong resemblance, especially for severe respiratory disturbance requiring mechanical ventilation at birth. After discharge from the hospital, 4 of the patients died of respiratory insufficiency within 1 or 2 weeks after birth, and 1 child died after 110 days of aggravated apnea. Apnea or respiratory failure was the main cause of early death in this family. Respiratory distress is a common manifestation of SHFYNG, especially...
Source: Molecular Syndromology - July 3, 2019 Category: Molecular Biology Source Type: research

Novel MECP2 Mutation c.1162_1172del; p.Pro388* in Two Patients with Symptoms of Atypical Rett Syndrome
We report 2 cases of girls withMECP2 gene variants who do not have typical clinical features of Rett syndrome except for intellectual disability and seizures. Both patients present with adipositas, macrocephalia, precocious puberty, and seizures. They have prominent eyebrows and a short neck as well as short and plump fingers. Sequencing by NGS revealed a novel variant c.1162_1172del; p.Pro388* in both patients.Mol Syndromol (Source: Molecular Syndromology)
Source: Molecular Syndromology - July 2, 2019 Category: Molecular Biology Source Type: research

Novel < b > < i > MECP2 < /i > < /b > Mutation c.1162_1172del; p.Pro388* in Two Patients with Symptoms of Atypical Rett Syndrome
We report 2 cases of girls withMECP2 gene variants who do not have typical clinical features of Rett syndrome except for intellectual disability and seizures. Both patients present with adipositas, macrocephalia, precocious puberty, and seizures. They have prominent eyebrows and a short neck as well as short and plump fingers. Sequencing by NGS revealed a novel variant c.1162_1172del; p.Pro388* in both patients.Mol Syndromol (Source: Molecular Syndromology)
Source: Molecular Syndromology - July 1, 2019 Category: Molecular Biology Source Type: research

Report of a Second Lebanese Family with Basel-Vanagaite-Smirin-Yosef Syndrome: Possible Founder Mutation?
Basel-Vanagaite-Smirin-Yosef syndrome (OMIM 616449) is a rare autosomal recessive genetic disorder characterized by severe developmental delay and variable craniofacial, neurological, cardiac, and ocular anomalies in the presence of variants in theMED25 gene. So far, only a handful of patients have been reported with this condition globally. Here, we report an additional Lebanese family with 2 affected siblings presenting with severely delayed psychomotor and language development as well as craniofacial anomalies. By whole-exome sequencing (WES), a homozygous variant was found in theMED25 gene, c.518T>C, predicted to re...
Source: Molecular Syndromology - June 27, 2019 Category: Molecular Biology Source Type: research

Concurrent Structural and Single Nucleotide Variation Resulting from a Single Replication-Based Mechanism
Mol Syndromol (Source: Molecular Syndromology)
Source: Molecular Syndromology - June 27, 2019 Category: Molecular Biology Source Type: research

Defining the Critical Region for Intellectual Disability and Brain Malformations in 6q27 Microdeletions
In conclusion, the 6q27 microdeletion is a complex syndrome with variable expressivity of brain malformations and intellectual disability phenotypes which are possibly triggered by the 4 genes described and adjacent genes susceptible to gene regulation changes.Mol Syndromol (Source: Molecular Syndromology)
Source: Molecular Syndromology - June 20, 2019 Category: Molecular Biology Source Type: research

A Balanced Reciprocal Translocation t(2;9)(p25;q13) Disrupting the LINC00299 Gene in a Patient with Intellectual Disability
Long intergenic noncoding RNAs (lincRNAs) are a class of noncoding RNAs implicated in several biological processes. LincRNA 299 (LINC00299) maps to 2p25.1 and its function is still unknown. However, this gene has been proposed as a candidate for intellectual disability (ID) in a patient with a balanced translocation where the breakpoint disrupted its ORF. Here, we describe a new case ofLINC00299 disruption associated with ID. The individual, a 42-year-old woman, was referred to the clinical geneticist because of her son who had severe syndromic ID. G-banding and chromosomal microarray analysis were performed. Karyotyping o...
Source: Molecular Syndromology - June 7, 2019 Category: Molecular Biology Source Type: research

A Balanced Reciprocal Translocation t(2;9)(p25;q13) Disrupting the < b > < i > LINC00299 < /i > < /b > Gene in a Patient with Intellectual Disability
Long intergenic noncoding RNAs (lincRNAs) are a class of noncoding RNAs implicated in several biological processes. LincRNA 299 (LINC00299) maps to 2p25.1 and its function is still unknown. However, this gene has been proposed as a candidate for intellectual disability (ID) in a patient with a balanced translocation where the breakpoint disrupted its ORF. Here, we describe a new case ofLINC00299 disruption associated with ID. The individual, a 42-year-old woman, was referred to the clinical geneticist because of her son who had severe syndromic ID. G-banding and chromosomal microarray analysis were performed. Karyotyping o...
Source: Molecular Syndromology - June 7, 2019 Category: Molecular Biology Source Type: research

Supravalvular Aortic Stenosis Caused by a Familial Chromosome 7 Inversion Disrupting the ELN Gene Uncovered by Whole-Genome Sequencing
We report herein the case of a 4-year-old boy presenting with clinically isolated supravalvular aortic stenosis (SVAS). No chromosomal imbalance was detected by array CGH. The karyotype showed a balanced paracentric chromosome 7 inversion. Breakpoint characterization using paired-end whole-genome sequencing (WGS) revealed anELNgene disruption in intron 1, accounting for the phenotype. Family study showed that the inversion was inherited, with incomplete penetrance. To our knowledge, this is the first case of a disruption of theELN gene characterized by WGS. It contributes to refine the genotype-phenotype correlation inELN ...
Source: Molecular Syndromology - May 24, 2019 Category: Molecular Biology Source Type: research

Supravalvular Aortic Stenosis Caused by a Familial Chromosome 7 Inversion Disrupting the < b > < i > ELN < /i > < /b > Gene Uncovered by Whole-Genome Sequencing
We report herein the case of a 4-year-old boy presenting with clinically isolated supravalvular aortic stenosis (SVAS). No chromosomal imbalance was detected by array CGH. The karyotype showed a balanced paracentric chromosome 7 inversion. Breakpoint characterization using paired-end whole-genome sequencing (WGS) revealed anELNgene disruption in intron 1, accounting for the phenotype. Family study showed that the inversion was inherited, with incomplete penetrance. To our knowledge, this is the first case of a disruption of theELN gene characterized by WGS. It contributes to refine the genotype-phenotype correlation inELN ...
Source: Molecular Syndromology - May 21, 2019 Category: Molecular Biology Source Type: research

Copy Number Gain at Xq28 in a Child with Global Developmental Delay Associated with a Variant Form of Hoyeraal-Hreidarsson Syndrome
We report the case of a child from Central Brazil with global developmental delay (GDD), syndromic features, and absence of abnormal skin pigmentation, nail dystrophy, and leukoplakia of the oral mucosa, with a rearrangement at Xq28 harboring theDKC1 gene. GTC-banding revealed a male karyotype (46,XY) with no visible numerical or structural alterations. Chromosomal microarray analysis (CMA) showed a 0.36-Mb gain at Xq28 of maternal origin, encompassing 22 genes, includingDKC1. Rearrangements and mutations involving this gene have been associated with dyskeratosis congenita, X-linked (OMIM 305000) and Hoyeraal-Hreidarsson s...
Source: Molecular Syndromology - April 26, 2019 Category: Molecular Biology Source Type: research

GATAD2B Gene Microdeletion Causing Intellectual Disability Autosomal Dominant Type 18: Case Report and Review of the Literature
This study highlights the importance of the phenotype-genotype correlation using molecular diagnostic techniques, such as CMA, and its impact on precise diagnosis, treatment, prognosis, and genetic counseling for patients and their families.Mol Syndromol (Source: Molecular Syndromology)
Source: Molecular Syndromology - April 16, 2019 Category: Molecular Biology Source Type: research

Novel HIVEP2 Variants in Patients with Intellectual Disability
Intellectual disability (ID) occurs in approximately 1% of the population. Over the last years, broad sequencing approaches such as whole exome sequencing (WES) substantially contributed to the definition of the molecular defects underlying nonsyndromic ID. Pathogenic variants inHIVEP2, which encodes the human immunodeficiency virus type I enhancer binding protein 2, have recently been reported as a cause of ID, developmental delay, behavioral disorders, and dysmorphic features. HIVEP2 serves as a transcriptional factor regulating NF-#x0138;B and diverse genes that are essential in neural development. To date, only 8 patie...
Source: Molecular Syndromology - April 16, 2019 Category: Molecular Biology Source Type: research

Phenotypic Spectrum and Severity of Disease Depending on the Mutated Protein Domain of NMDA Receptor-Encoding Genes
Mol Syndromol (Source: Molecular Syndromology)
Source: Molecular Syndromology - April 16, 2019 Category: Molecular Biology Source Type: research

< b > < i > GATAD2B < /i > < /b > Gene Microdeletion Causing Intellectual Disability Autosomal Dominant Type 18: Case Report and Review of the Literature
This study highlights the importance of the phenotype-genotype correlation using molecular diagnostic techniques, such as CMA, and its impact on precise diagnosis, treatment, prognosis, and genetic counseling for patients and their families.Mol Syndromol (Source: Molecular Syndromology)
Source: Molecular Syndromology - April 16, 2019 Category: Molecular Biology Source Type: research

Novel < b > < i > HIVEP2 < /i > < /b > Variants in Patients with Intellectual Disability
Intellectual disability (ID) occurs in approximately 1% of the population. Over the last years, broad sequencing approaches such as whole exome sequencing (WES) substantially contributed to the definition of the molecular defects underlying nonsyndromic ID. Pathogenic variants inHIVEP2, which encodes the human immunodeficiency virus type I enhancer binding protein 2, have recently been reported as a cause of ID, developmental delay, behavioral disorders, and dysmorphic features. HIVEP2 serves as a transcriptional factor regulating NF-#x0138;B and diverse genes that are essential in neural development. To date, only 8 patie...
Source: Molecular Syndromology - April 3, 2019 Category: Molecular Biology Source Type: research

Torpedo Maculopathy Associated with NEXMIF Mutation
Mutations in the neurite extension and migration factor (NEXMIF) gene are associated with X-linked intellectual disability. Thus far, all males reported withNEXMIF mutations have mild to profound intellectual disability with varying combinations of autistic features, poor or absent speech, epilepsy, facial dysmorphism, and strabismus. Affected females tend to have milder intellectual disability but severe, drug-resistant epilepsy. Here, we present a 32-month-old boy with a novel de novo frameshiftNEXMIF pathogenic variant (p.Glu375ArgfsX21) who has mild motor delay, language delay, autistic features, and strabismus. In add...
Source: Molecular Syndromology - March 21, 2019 Category: Molecular Biology Source Type: research

Blepharophimosis, Ptosis, Epicanthus Inversus Syndrome: New Report with a 197-kb Deletion Upstream of < b > < i > FOXL2 < /i > < /b > and Review of the Literature
In this study, a prepubertal girl with BPES due to a 197-kb de novo deletion of the regulatory elements upstream ofFOXL2is reported.This girl presented with additional clinical features such as a soft cleft palate and microcephaly; thus, this copy number variant might have other somatic effects. The present deletion encompasses 2 coding genes (MRPS22andCOPB2), whose homozygous mutations have been associated with microcephaly. In our case, the sequences of the non-deleted allele were normal, ruling out a compound genetic defect. Normal levels of new biomarkers of ovarian reserve (anti-m üllerian hormone, inhibin B) lik...
Source: Molecular Syndromology - March 21, 2019 Category: Molecular Biology Source Type: research

Torpedo Maculopathy Associated with < b > < i > NEXMIF < /i > < /b > Mutation
Mutations in the neurite extension and migration factor (NEXMIF) gene are associated with X-linked intellectual disability. Thus far, all males reported withNEXMIF mutations have mild to profound intellectual disability with varying combinations of autistic features, poor or absent speech, epilepsy, facial dysmorphism, and strabismus. Affected females tend to have milder intellectual disability but severe, drug-resistant epilepsy. Here, we present a 32-month-old boy with a novel de novo frameshiftNEXMIF pathogenic variant (p.Glu375ArgfsX21) who has mild motor delay, language delay, autistic features, and strabismus. In add...
Source: Molecular Syndromology - March 15, 2019 Category: Molecular Biology Source Type: research

Deletion of Chromosome 13 due to Different Rearrangements and Impact on Phenotype
Patients with deletion of chromosome 13 present with variable clinical features, and the correlation between phenotype and genomic aberration is not well established in the literature, mainly due to variable sizes of the deleted segments and inaccuracy of breakpoint mapping. In order to improve the genotype-phenotype correlation, we obtained clinical and cytogenomic data from 5 Brazilian patients with different chromosome 13 deletions characterized by G-banding and array techniques. Breakpoints were nonrecurrent, with deletion sizes ranging from 3.8 to 43.3 Mb. Our patients showed some classic features associated with 13q ...
Source: Molecular Syndromology - March 8, 2019 Category: Molecular Biology Source Type: research

Further Delineation of the Microcephaly-Micromelia Syndrome Associated with Loss-of-Function Variants in DONSON
TheDONSON gene encodes the downstream neighbor of SON, a replisome component that stabilizes the replication fork during replication. A severe form of microcephalic dwarfism, microcephaly-micromelia syndrome (MIMIS), has been recently associated withDONSON biallelic loss of function. Affected fetuses suffer severe growth restriction, microcephaly, and variable limb malformations which result in intrauterine or perinatal death. All described fetuses carried a homozygous founder mutation (c.1047-9A>G), a splice-altering variant that leads to transcript degradation. We evaluated 2 newborns from a consanguineous Emirati fam...
Source: Molecular Syndromology - March 8, 2019 Category: Molecular Biology Source Type: research

Subject Index
Mol Syndromol 2019;10:125-126 (Source: Molecular Syndromology)
Source: Molecular Syndromology - February 22, 2019 Category: Molecular Biology Source Type: research

Author Index
Mol Syndromol 2019;10:124 (Source: Molecular Syndromology)
Source: Molecular Syndromology - February 22, 2019 Category: Molecular Biology Source Type: research

Title Page / Table of Contents
Mol Syndromol 2019;10:1-4 (Source: Molecular Syndromology)
Source: Molecular Syndromology - February 22, 2019 Category: Molecular Biology Source Type: research

A Venezuelan Case of Schmid-Type Metaphyseal Chondrodysplasia with a Novel Mutation in COL10A1
We report an 8-year-old girl with waddling gait, short stature, mild dorsal scoliosis, coxa vara, short lower limbs, bowing of the femurs, genu varum, and metaphyseal fraying and splaying, who is a carrier of a novel heterozygous 2-bp (c.1894_1895dupTA; p.Leu633Thrf s*45) duplication in exon 3 of theCOL10A1gene.Mol Syndromol (Source: Molecular Syndromology)
Source: Molecular Syndromology - February 12, 2019 Category: Molecular Biology Source Type: research

A Venezuelan Case of Schmid-Type Metaphyseal Chondrodysplasia with a Novel Mutation in < b > < i > COL10A1 < /i > < /b >
We report an 8-year-old girl with waddling gait, short stature, mild dorsal scoliosis, coxa vara, short lower limbs, bowing of the femurs, genu varum, and metaphyseal fraying and splaying, who is a carrier of a novel heterozygous 2-bp (c.1894_1895dupTA; p.Leu633Thrf s*45) duplication in exon 3 of theCOL10A1gene.Mol Syndromol (Source: Molecular Syndromology)
Source: Molecular Syndromology - February 8, 2019 Category: Molecular Biology Source Type: research

Co-Occurrence of Leber Congenital Amaurosis and Meckel Syndrome Type 1 in a Fetus: Is There a Lesson to Be Learned?
A patient referred for prenatal diagnostics, after first-trimester ultrasound due to a previous child with Leber congenital amaurosis, was suggestive of a Meckel syndrome-like phenotype. Fetal autopsy confirmed the multiple anomalies, and whole-exome sequencing of the fetal DNA identified a pathogenic variant in theRPGRIP1 gene, previously identified in the elder sibling, and a variant causative of Meckel syndrome 1 in theMKS1gene. Reporting theMKS1 mutation, which was present in heterozygous state in the elder sibling, as a secondary finding would have enabled the parents to be tested for carrier status of the same varian...
Source: Molecular Syndromology - January 22, 2019 Category: Molecular Biology Source Type: research

1q42.12q42.2 Deletion in a Child with Midline Defects and Hypoplasia of the Corpus Callosum
In this report, we detected a 5.8-Mb deletion encompassing the chromosome 1q42.12q42.2 region in a 4-year-old boy with hypoplastic corpus callosum, epilepsy, developmental delay, microcephaly, cata ract, cleft palate, and skeletal changes. The deletion was de novo. Genotype-phenotype correlations suggest that the major features of 1q42.12q42.2 microdeletion were attributed to the genes with a high probability of loss-of-function intolerance score in this deletion, namelyLBR, ENAH, ACBD3, LIN9, ITPKB, CDC42BPA, ARF1, TAF5L, GALNT2, SPRTN, andEGLN1along with GNPAT.Mol Syndromol (Source: Molecular Syndromology)
Source: Molecular Syndromology - January 15, 2019 Category: Molecular Biology Source Type: research

Syndromic Craniosynostosis: Complexities of Clinical Care
Patients with syndromic craniosynostosis have a molecularly identified genetic cause for the premature closure of their cranial sutures and associated facial and extra-cranial features. Their clinical complexity demands comprehensive management by an extensive multidisciplinary team. This review aims to marry genotypic and phenotypic knowledge with clinical presentation and management of the craniofacial syndromes presenting most frequently to the craniofacial unit at Great Ormond Street Hospital for Children NHS Foundation Trust.Mol Syndromol 2019;10:79-93 (Source: Molecular Syndromology)
Source: Molecular Syndromology - January 15, 2019 Category: Molecular Biology Source Type: research

< b > < i > HNRNPU < /i > < /b > : Key to Neurodevelopmental Disorders such as Intellectual Delay, Epilepsy, and Autism
Mol Syndromol 2018;9:275-278 (Source: Molecular Syndromology)
Source: Molecular Syndromology - January 14, 2019 Category: Molecular Biology Source Type: research

Novel Mutations and Unreported Clinical Features in KBG Syndrome
We report 12 unrelated patients where a clinical diagnosis of KBG was suspected and confirmed by targeted analyses. Nine patients showed a point mutation inANKRD11 (none of which were previously reported) and 3 carried a 16q24.3 deletion. All patients presented with typical facial features and macrodontia. Skeletal abnormalities were constant, and the majority of patients showed joint stiffness. Three patients required growth hormone treatment with a significant increase of height velocity. Brain malformations were identified in 8 patients. All patients showed behavioral abnormalities and most had developmental delay. Two ...
Source: Molecular Syndromology - January 14, 2019 Category: Molecular Biology Source Type: research

Combined Phenotypes of Spondylometaphyseal Dysplasia-Kozlowski Type and Charcot-Marie-Tooth Disease Type 2C Secondary to a < b > < i > TRPV4 < /i > < /b > Pathogenic Variant
We present an additional patient who has an overlapping neuromuscular and skeletal phenotype secondary to aTRPV4 pathogenic variant. The patient has spondylometaphyseal dysplasia-Kozlowski type and Charcot-Marie-Tooth disease type 2C. This and prior reports illustrate thatTRPV4-related skeletal dysplasias andTRPV4-related neuropathies are not fully distinct disorders secondary to unique sets of pathogenic variants as originally postulated, but rather are 2 phenotypes on the same spectrum that may or may not overlap. We suggest that evaluation for patients presenting with anyTRPV4-related disorder include assessment for bot...
Source: Molecular Syndromology - December 20, 2018 Category: Molecular Biology Source Type: research

Extending the Phenotype and Identification of a Novel Candidate Gene for Immunodeficiency in 5q11 Microdeletion Syndrome
We present a patient with a 7-Mb deletion at 5q11.2 with previously unreported features, such as immunodeficiency, asymmetry of hands and feet, joint laxity, and agenesis of corpus callosum. The clinical features of this patient are compared with 13 patients reported previously. A common critical region (CCR) of 1.4 Mb (54-55.4 Mb) is defined in all cases including the present one. Of the 14 genes present in CCR,IL6ST is proposed to be the candidate gene for immunodeficiency observed in some of these patients.IL6ST encodes gp130, a signal transduction protein for various interleukins and cytokines. It is involved in the ge...
Source: Molecular Syndromology - December 20, 2018 Category: Molecular Biology Source Type: research

HNRNPU: Key to Neurodevelopmental Disorders such as Intellectual Delay, Epilepsy, and Autism
Mol Syndromol (Source: Molecular Syndromology)
Source: Molecular Syndromology - November 30, 2018 Category: Molecular Biology Source Type: research

8p11 Microduplication Is Associated with Neonatal Stridor
We report a term male infant with congenital stridor secondary to tracheomalacia and a mild coarctation of the aorta. Developmental delay was noted upon follow-up. Whole genome SNP microarray analysis showed an ∼846-kb interstitial duplication of the short arm of chromosome 8 (8p11.21p11.1). We report novel clinical findings of this rare genetic condition.Mol Syndromol (Source: Molecular Syndromology)
Source: Molecular Syndromology - November 20, 2018 Category: Molecular Biology Source Type: research

Current Approaches in the Development of Molecular and Pharmacological Therapies in Craniosynostosis Utilizing Animal Models
The development of the craniofacial skeleton is a spatial and temporal process where cranial sutures play a role in the regulation of morphogenesis and growth. Disruption of these cellular and molecular interactions may lead to craniosynostosis, the premature obliteration of one or more cranial sutures, yielding skull growth restriction and malformation perpendicular to the affected suture. Facial deformity and various functional CNS anomalies are other frequent complications. Cranial vault expansion and reconstructive surgery remain the mainstay of treatment but pose an elevated risk of morbidity for the infant. While the...
Source: Molecular Syndromology - November 16, 2018 Category: Molecular Biology Source Type: research

17p13.1 Microduplication Syndrome in a Child, Familial Short Stature, and Growth Hormone Deficiency: A Case Report and Review of the Literature
We describe the first case of a young patient with a maternally inherited microduplication in 17p13.1 presenting with growth hormone deficiency. The boy was addressed to the endocrine division for growth retardation (weight and height (Source: Molecular Syndromology)
Source: Molecular Syndromology - November 15, 2018 Category: Molecular Biology Source Type: research

Distal Arthrogryposis with Impaired Proprioception and Touch: Description of an Early Phenotype in a Boy with Compound Heterozygosity of < b > < i > PIEZO2 < /i > < /b > Mutations and Review of the Literature
The recessivePIEZO2-associated disease, distal arthrogryposis with impaired proprioception and touch (DAIPT), is characterized by hypotonia, perinatal respiratory distress, significantly delayed motor milestones, and progressive symptoms of distal arthrogryposis and scoliosis. Here, we describe the youngest patient with DAIPT to date, who, at the age of 3.5 years, did not show a single clinical sign of distal arthrogryposis or contractures, but had a history of bilateral clubfoot operations. On the contrary, he presented with some features, not described thus far, such as syringohydromyelia, a small cyst of the spinal cord...
Source: Molecular Syndromology - November 12, 2018 Category: Molecular Biology Source Type: research

COQ8A and MED25 Mutations in a Child with Intellectual Disability, Microcephaly, Seizures, and Spastic Ataxia: Synergistic Effect of Digenic Variants
We report on a girl, born to first-cousin Lebanese parents, with severe intellectual disability, congenital hip luxation, cardiac malformation, short stature, facial dysmorphic features including microcephaly, sparse hair, bilateral epicanthal folds, ataxia, seizures, and elevated lactate and pyruvate levels in serum. Whole exome sequencing was carried out on the patient's DNA. Potentially causal homozygous variants in theMED25(p.Ile173Thr) andCOQ8A (p.Arg512Trp) genes were found. The potential pathogenicity of these variants, and the possibility that the 2 variants could synergistically act to produce the phenotype report...
Source: Molecular Syndromology - November 9, 2018 Category: Molecular Biology Source Type: research

Thrombocytopenia and Predisposition to Acute Myeloid Leukemia due to Mosaic Ring 21 with Loss of RUNX1: Cytogenetic and Molecular Characterization
Familial platelet disorder with predisposition to acute myeloid leukemia (FPD/AML) has been well documented in the literature and is a new entity within the latest revised edition of the WHO Classification of Tumors of Hematopoietic and Lymphoid Tissues (OMIM). The disorder arises due to mutations within theRUNX1 gene in chromosome 21; mutations within the Runt-binding domain are the most commonly encountered anomalies that cause decreased platelet count and function. Rare cases of haploinsufficiency have also been shown to cause this disorder. Here, we describe a 12-year-old female with mosaicism for a ring chromosome 21 ...
Source: Molecular Syndromology - November 9, 2018 Category: Molecular Biology Source Type: research

< b > < i > COQ8A < /i > < /b > and < b > < i > MED25 < /i > < /b > Mutations in a Child with Intellectual Disability, Microcephaly, Seizures, and Spastic Ataxia: Synergistic Effect of Digenic Variants?
We report on a girl, born to first-cousin Lebanese parents, with severe intellectual disability, congenital hip luxation, cardiac malformation, short stature, facial dysmorphic features including microcephaly, sparse hair, bilateral epicanthal folds, ataxia, seizures, and elevated lactate and pyruvate levels in serum. Whole exome sequencing was carried out on the patient's DNA. Potentially causal homozygous variants in theMED25(p.Ile173Thr) andCOQ8A (p.Arg512Trp) genes were found. The potential pathogenicity of these variants, and the possibility that the 2 variants could synergistically act to produce the phenotype report...
Source: Molecular Syndromology - November 8, 2018 Category: Molecular Biology Source Type: research

Thrombocytopenia and Predisposition to Acute Myeloid Leukemia due to Mosaic Ring 21 with Loss of < b > < i > RUNX1 < /i > < /b > : Cytogenetic and Molecular Characterization
Familial platelet disorder with predisposition to acute myeloid leukemia (FPD/AML) has been well documented in the literature and is a new entity within the latest revised edition of the WHO Classification of Tumors of Hematopoietic and Lymphoid Tissues (OMIM). The disorder arises due to mutations within theRUNX1 gene in chromosome 21; mutations within the Runt-binding domain are the most commonly encountered anomalies that cause decreased platelet count and function. Rare cases of haploinsufficiency have also been shown to cause this disorder. Here, we describe a 12-year-old female with mosaicism for a ring chromosome 21 ...
Source: Molecular Syndromology - November 8, 2018 Category: Molecular Biology Source Type: research

Identification of an Autosomal Dominant Mutation in the < b > < i > COL2A1 < /i > < /b > Gene Leading to Spondyloepiphyseal Dysplasia Congenita in a Greek Family
In conclusion, we describe a patient with hereditary spondyloepiphyseal dysplasia congenita, caused by a c.1609G_A (p.Gly537Ser) mutation in theCOL2A1 gene, which resulted in a milder phenotype.Mol Syndromol 2018;9:241-246 (Source: Molecular Syndromology)
Source: Molecular Syndromology - November 7, 2018 Category: Molecular Biology Source Type: research

Paving the Way for Therapy: The Second International Conference of the Trisomy 21 Research Society
In the last decade, a number of important research advances in different fields have allowed Down syndrome (DS) research to flourish, creating a time of both unparalleled opportunity and considerable challenge. Building a scientific framework that distills mechanisms involved in the developmental intellectual disability of DS as well as the early-onset component of Alzheimer disease and the several other comorbidities associated with the condition is a challenge that scientists are now tackling using novel technologies and multidisciplinary approaches. The Trisomy 21 Research Society (T21RS) was founded in 2014 to address ...
Source: Molecular Syndromology - October 29, 2018 Category: Molecular Biology Source Type: research

Michael Schmid (1948-2018): A Life Devoted to Science
Mol Syndromol (Source: Molecular Syndromology)
Source: Molecular Syndromology - October 16, 2018 Category: Molecular Biology Source Type: research

The Osteogenic Potential of the Neural Crest Lineage May Contribute to Craniosynostosis
The craniofacial skeleton is formed from the neural crest and mesodermal lineages, both of which contribute mesenchymal precursors during formation of the skull bones. The large majority of cranial sutures also includes a proportion of neural crest-derived mesenchyme. While some studies have addressed the relative healing abilities of neural crest and mesodermal bone, relatively little attention has been paid to differences in intrinsic osteogenic potential. Here, we use mouse models to compare neural crest osteoblasts (from frontal bones or dura mater) to mesodermal osteoblasts (from parietal bones). Using in vitro cultur...
Source: Molecular Syndromology - October 12, 2018 Category: Molecular Biology Source Type: research

Microcephaly/Trigonocephaly, Intellectual Disability, Autism Spectrum Disorder, and Atypical Dysmorphic Features in a Boy with Xp22.31 Duplication
This report provides further insight into the pathogenicity of the Xp22.31 duplication by extending knowledge of its clinical features. This case, in association with those reported in the literature, indicates that the Xp22.31 duplication may contribute to cause pathological phenotypes with minor facial dysmorphisms, microcephaly, and intellectual disability as main features.Mol Syndromol (Source: Molecular Syndromology)
Source: Molecular Syndromology - October 5, 2018 Category: Molecular Biology Source Type: research

Understanding Craniosynostosis: Clinical Practice to Basic Science
Mol Syndromol (Source: Molecular Syndromology)
Source: Molecular Syndromology - September 11, 2018 Category: Molecular Biology Source Type: research

Identification of an Autosomal Dominant Mutation in the COL2A1 Gene Leading to Spondyloepiphyseal Dysplasia Congenita in a Greek Family
In conclusion, we describe a patient with hereditary spondyloepiphyseal dysplasia congenita, caused by a c.1609G_A (p.Gly537Ser) mutation in theCOL2A1 gene, which resulted in a milder phenotype.Mol Syndromol (Source: Molecular Syndromology)
Source: Molecular Syndromology - September 3, 2018 Category: Molecular Biology Source Type: research

Clinical Transcriptome Sequencing Confirms Activation of a Cryptic Splice Site in Suspected SYNGAP1-Related Disorder
This report highlights the utility of functional studies newly available to clinical practice in confirming a suspected genetic diagnosis, which can directly impact medical management and preclude the need for additional diagnostic testing.Mol Syndromol (Source: Molecular Syndromology)
Source: Molecular Syndromology - August 27, 2018 Category: Molecular Biology Source Type: research