Wiedemann-Steiner Syndrome as a Differential Diagnosis of Cornelia de Lange Syndrome Using Targeted Next-Generation Sequencing: A Case Report
Wiedemann-Steiner syndrome (WDSTS) is a rare autosomal dominant disorder with a variable clinical phenotype including synophrys, hypertelorism, thick eyebrows, long eyelashes, wide nasal bridge, long philtrum, hypertrichosis, growth retardation, and intellectual disability. Cornelia de Lange syndrome (CdLS) is a rare disease characterized by synophrys, long eyelashes, limb abnormalities, generalized hirsutism, growth retardation, and intellectual disability. In both WDSTS and CdLS, the malformations are due to transcriptome disturbance caused by defects in the genes encoding the components of chromatin regulation and trans...
Source: Molecular Syndromology - December 1, 2020 Category: Molecular Biology Source Type: research

Novel Findings in Floating-Harbor Syndrome and a Mini-Review of the Literature
Floating-Harbor syndrome (FHS) is a rare autosomal dominant genetic disorder characterized by proportionate short stature with delayed bone maturation, lack of expressive language, and distinctive facial features including a large nose, long eyelashes, deeply set eyes, and triangular face. Mutations in theSRCAP gene cause truncated SNF2-related CREBBP activator protein (SRCAP) and lead to FHS. SRCAP is one of several proteins that act as coactivator for the CREB-binding protein which is associated with Rubinstein-Taybi syndrome (RSTS). This condition likely explains the phenotypic overlap between FHS and RSTS. Herein, we r...
Source: Molecular Syndromology - November 30, 2020 Category: Molecular Biology Source Type: research

Clinical and Molecular Spectrum of Four Patients Diagnosed with Mowat-Wilson Syndrome
In this study, we aimed to evaluate the clinical features and molecular analysis results of 4 MWS patients. All patients were examined by an expert clinical geneticist. Dysmorphological abnormalities were recorded. Data including demographic, clinical, and laboratory findings were obtained from hospital records.ZEB2 gene analysis was performed using a Sanger sequencing method. All patients had typical facial features of MWS such as widely spaced eyes, broad eyebrows with a medial flare, low-hanging columella, prominent or pointed chin, open-mouth expression, and uplifted earlobes. Four different heterozygous mutations were...
Source: Molecular Syndromology - November 20, 2020 Category: Molecular Biology Source Type: research

Phenotypic Characteristics and Copy Number Variants in a Cohort of Colombian Patients with VACTERL Association
In this study, the clinical phenotype and its relationship with the presence of chromosomal abnormalities and FA were evaluated in 18 patients with VACTERL association. For this, a G-banded karyotype, array-comparative genomic hybridization, and chromosomal fragility test for FA were performed. All patients (10 female and 8 male) showed a broad clinical spectrum: 13 (72.2%) had vertebral abnormalities, 8 (44.4%) had anal atresia, 14 (77.8%) had heart defects, 8 (44.4%) had esophageal atresia, 10 (55.6%) had renal abnormalities, and 10 (55.6%) had limb defects. Chromosomal abnormalities and FA were ruled out. In 2 cases, th...
Source: Molecular Syndromology - November 11, 2020 Category: Molecular Biology Source Type: research

A Case of UDP-Galactose 4 ′-Epimerase Deficiency Associated with Dyshematopoiesis and Atrioventricular Valve Malformations: An Exceptional Clinical Phenotype Explained by Altered N-Glycosylation with Relative Preservation of the Leloir Pathway
We report a 2-year-old child compound heterozygous for GALE p.R51W/p.G237D who never developed symptoms of classic galactosemia but has a history of congenital combined mitral and tricuspid valve malformation and pyloric stenosis, and presented with pancytopenia. Variant pathogenicity was supported by predictive computational tools and decreased GALE activity measured in erythrocytes. GALE function e xtends to the biosynthesis of glycans by epimerization of UDP-N-acetyl-galactosamine and -glucosamine. Interrogation of the Gene Ontology consortium database revealed several putative proteins involved in normal hematopoiesis ...
Source: Molecular Syndromology - October 29, 2020 Category: Molecular Biology Source Type: research

Fanconi Anemia: A Syndrome of Anemia and Skeletal Malformations Progressing to a Gene Network Involved in Genomic Stability and Malignant Disease
Mol Syndromol (Source: Molecular Syndromology)
Source: Molecular Syndromology - October 22, 2020 Category: Molecular Biology Source Type: research

Publisher's Note
Mol Syndromol (Source: Molecular Syndromology)
Source: Molecular Syndromology - October 19, 2020 Category: Molecular Biology Source Type: research

A Novel < b > < i > ELP2 < /i > < /b > Compound Heterozygous Mutation in a Boy with Severe Intellectual Disability, Spastic Diplegia, Stereotypic Behavior and Review of the Current Literature
We present this case report to clarify the clinical findings of a very rare neurodevelopmental phenotype and to contribute new information to the current literature on genotype-phenotype correlations.Mol Syndromol (Source: Molecular Syndromology)
Source: Molecular Syndromology - October 15, 2020 Category: Molecular Biology Source Type: research

Application of Chromosome Microarray Analysis in the Investigation of Developmental Disabilities and Congenital Anomalies: Single Center Experience and Review of < b > < i > NRXN3 < /i > < /b > and < b > < i > NEDD4L < /i > < /b > Deletions
This study showed that CMA is a powerful diagnostic tool in this patient group and expands the genotype-phenotype correlations on developmental disabilities.Mol Syndromol (Source: Molecular Syndromology)
Source: Molecular Syndromology - October 5, 2020 Category: Molecular Biology Source Type: research

Eyes See what the Mind Knows: Clues to Pattern Recognition in Single Enzyme Deficiency-Related Peroxisomal Disorders
We present 3 molecularly confirmed families: 1 with Acyl CoA oxidase deficiency and 2 with D-bifunctional protein deficiency. The clinical, biochemical, and radiological features of these patients have been discussed. We attempt to highlight the overlap in facial features as well as strikingly similar MRI findings of cerebellar atrophy and white matter hyperintensities. This unique clinical profile will not only help in reaching a quick diagnosis, but in this era of variants of uncertain significance, it will prove as supporting evidence. Finally, we expand the genotypic spectrum with a description of 3 homozygous novel mu...
Source: Molecular Syndromology - September 30, 2020 Category: Molecular Biology Source Type: research

Clinical and Molecular Characterization of Fanconi Anemia Patients in Turkey
Fanconi anemia (FA) is a rare multigenic chromosomal instability syndrome that predisposes patients to life-threatening bone marrow failure, congenital malformations, and cancer. Functional loss of interstrand cross-link (ICL) DNA repair system is held responsible, though the mechanism is not yet fully understood. The clinical and molecular findings of 20 distinct FA cases, ages ranging from perinatal stage to 32 years, are presented here. Pathogenic variants inFANCA were found responsible in 75%,FANCC,FANCE,FANCJ/BRIP1,FANCL in 5%, andFANCD1/BRCA2 andFANCN/PALB2 in 2.5% of the subjects. Altogether, 25 different variants i...
Source: Molecular Syndromology - September 23, 2020 Category: Molecular Biology Source Type: research

Phenotypic and Molecular Cytogenetic Analysis of a Case of Monosomy 1p36 Syndrome due to Unbalanced Translocation
Monosomy 1p36 syndrome is one of the most common submicroscopic deletion syndromes, which is characterized by the presence of delayed developmental milestones, intellectual disability, and clinically recognizable dysmorphic craniofacial features. The syndrome comprises 4 cytogenetic groups including pure terminal deletions, interstitial deletions, complex rearrangements, and derivative chromosomes 1 due to unbalanced translocations, where unbalanced translocations represent the least percentage of all cases of monosomy 1p36 (7%). Most patients with monosomy 1p36 due to an unbalanced translocation can be cytogenetically dia...
Source: Molecular Syndromology - September 23, 2020 Category: Molecular Biology Source Type: research

Hyperinsulinemic Hypoglycemia in a Patient with Costello Syndrome: An Etiology to Consider in Hypoglycemia
In this report, we describe a patient with CS accompanied by a clinical picture of hyperinsulinemic hypoglycemia responsive to diazoxide treatment. A 41-day-old female patient with a birth weight of 3,600 g was referred for atypical facial features and swallowing dysfunction. She had a weight of 4,000 g ( −0.8 SDS), a length of 50 cm (−2.4 SDS), and a head circumference of 38 cm (0.2 SDS). The clinical findings were suggestive of a genetic syndrome, mainly a RASopathy or Beckwith-Wiedemann syndrome. Whole exome sequencing revealed a de novo heterozygous missense variant in theHRAS (NM_001130442) gene in exon 2:...
Source: Molecular Syndromology - September 16, 2020 Category: Molecular Biology Source Type: research

A Deep Intronic Variant Activates a Pseudoexon in the < b > < i > MTM1 < /i > < /b > Gene in a Family with X-Linked Myotubular Myopathy
We report a novel intronic variant in theMTM1 gene in 4 males in a family with severe X-linked myotubular myopathy. The A#x3e;G variant in deep intronic space activates a cryptic 5 ′ donor splice site resulting in the inclusion of a 48-bp pseudoexon into the matureMTM1 mRNA. The variant is present in all affected males, absent in unaffected males, and heterozygous in the mother of the affected males. The included intronic sequence contains a premature stop codon, and experiments using a translational inhibitor indicate that the mutant mRNAs undergo nonsense-mediated decay. We conclude that affected males produce no, ...
Source: Molecular Syndromology - September 16, 2020 Category: Molecular Biology Source Type: research

First Infertile Case with < b > < i > CSTF2T < /i > < /b > Gene Mutation
Male infertility is multifactorial and presents with heterogeneous phenotypic features. Genetic factors are responsible for up to 15% of the male infertility cases. Loss of theCstf2t gene in male mice results in infertility. No disease-associated mutations have been described for this gene in infertile men. Here, we report a patient diagnosed with infertility in whom a homozygous nonsense mutation in theCSTF2T gene was detected by clinical exome sequencing. This case is the first description of an infertile patient who has a homozygousCSTF2T mutation.Mol Syndromol (Source: Molecular Syndromology)
Source: Molecular Syndromology - September 14, 2020 Category: Molecular Biology Source Type: research

A Case of Ring Chromosome 18 with Single Umbilical Artery Detected During Prenatal Period
In this study, the clinical findings of a female patient who had a single umbilical artery in the prenatal period and was diagnosed as de novo r(18) by molecular karyotype analysis were compared with those in the literature. A detailed ultrasonographic examination of the fetus with a single umbilical artery may enable the detection of additional anomalies and thus the early diagnosis of chromosomal anomalies may be possible with prenatal genetic analysis.Mol Syndromol (Source: Molecular Syndromology)
Source: Molecular Syndromology - September 10, 2020 Category: Molecular Biology Source Type: research

Molecular Etiology of Isolated Congenital Cataract Using Next-Generation Sequencing: Single Center Exome Sequencing Data from Turkey
In this study, we aimed to identify and discuss the molecular etiology of nonsyndromic or nonmetabolic bilateral congenital cataract by whole-exome sequencing (WES). Patients with bilateral congenital cataract presumed to be isolated after metabolic and genetic evaluation were enrolled in the study. All patients underwent detailed ophthalmological examination and bilateral cataract surgery. DNA samples of the probands, parents, and available affected family members were analyzed by WES. Variants were validated and confirmed by Sanger sequencing in all probands and in available affected family members. A total of 4 patients...
Source: Molecular Syndromology - September 9, 2020 Category: Molecular Biology Source Type: research

Intrauterine Growth Restriction and Hypertrophic Cardiomyopathy as Prenatal Ultrasound Findings in a Case of Leprechaunism
We report the case of a 29-year-old pregnant woman, primigravida, who was referred at 33 weeks of gestation for severe intrauterine growth restriction (IUGR). Ultrasound examination found severe IUGR associated with an obstructive hypertrophic cardiomyopathy (HCM), confirmed postnatally. The newborn ’s blood glucose level fluctuated from fasting hypoglycemia to postprandial hyperglycemia. The infant was found to be homozygous for a novel missense pathogenic variant, c.632C#x3e;T (p.T211l), in exon 2 of theINSR gene, predicted to result in an abnormal insulin receptor. To our knowledge, this is the first report of lep...
Source: Molecular Syndromology - September 2, 2020 Category: Molecular Biology Source Type: research

Clonazepam as an Effective Treatment for Epilepsy in a Female Patient with < b > < i > NEXMIF < /i > < /b > Mutation: Case Report
We report a female patient with a heterozygous de novo mutation, NM_001008537.2:c.1123del (p.Glu375Argfs*21), inNEXMIF. The patient showed mild intellectual disability, facial dysmorphism, obesity, generalized tonic-clonic seizures, and nonconvulsive status epilepticus. Sodium valproate was effective but caused secondary amenorrhea. We successfully treated her epilepsy with clonazepam without side effects, indicating that clonazepam might be a good choice to treat epilepsy in patients withNEXMIF mutations.Mol Syndromol (Source: Molecular Syndromology)
Source: Molecular Syndromology - September 1, 2020 Category: Molecular Biology Source Type: research

3-Hydroxyisobutyryl-CoA Hydrolase Deficiency in a Turkish Child with a Novel < b > < i > HIBCH < /i > < /b > Gene Mutation and Literature Review
We report a 12-month-old severely affected female infant with a novel homozygous c.556C>G; p.R186G variant in theHIBCH gene presenting with axial hypotonia, severe developmental delay, and brain lesions in the basal ganglia and provide an overview of the literature. When suspected, newborn and selective screening with tandem mass analyses should include hydroxy-C4-carnitine to diagnose this disorder. However, in some cases, mostly in those with milder phenotype, diagnosis may be missed due to normal hydroxy-C4 carnitine levels.Mol Syndromol 2020;11:170-175 (Source: Molecular Syndromology)
Source: Molecular Syndromology - June 15, 2020 Category: Molecular Biology Source Type: research

Coffin-Siris Syndrome 4-Related Spectrum in a Young Woman Caused by a Heterozygous < b > < i > SMARCA4 < /i > < /b > Deletion Detected by High-Resolution aCGH
Coffin-Siris Syndrome 4 is an autosomal dominant congenital malformation syndrome caused by heterozygous mutations in theSMARCA4 gene with its main features being intellectual disability, developmental delay, behavioral abnormalities, and hypoplastic or absent fifth fingernails and fifth distal phalanges. Here, we report a young woman with developmental delay, moderate intellectual disability, and bilateral sensorineural hearing loss, referred for genetic testing. High-resolution chromosomal microarray analysis identified a 428-kb deletion in chromosome 19 which included theSMARCA4 gene. We conclude that haploinsufficiency...
Source: Molecular Syndromology - June 12, 2020 Category: Molecular Biology Source Type: research

A Novel de novo Frameshift Mutation in the < b > < i > BCL11A < /i > < /b > Gene in a Patient with Intellectual Disability Syndrome and Epilepsy
Intellectual disability syndrome (IDS) associated with a hereditary persistence of fetal haemoglobin (HbF), also known as Dias-Logan syndrome, is commonly characterised by psychomotor developmental delay, intelectual disability, language delay, strabismus, thin upper lip, abnormalities of external ears, microcephaly, downslanting palpebral fissures. Sporadically, autism spectrum disorders and blue sclerae in infancy have been reported in IDS. Rarely, IDS-affected patients present with epilepsy and/or epileptic syndromes. It has been shown that a haploinsufficiency of the B cell leukaemia/lymphoma 11A gene (BCL11A) is respo...
Source: Molecular Syndromology - June 12, 2020 Category: Molecular Biology Source Type: research

Distal 3p Duplication and 22q13.3 Deletion with Severe Hypotonia Originating from a Paternal Balanced Translocation (3;22)
In this study, we present a case with distal 3p duplication and 22q13.3 deletion due to unbalanced meiotic segregation in her father carrying a balanced translocation. The 2-month-old girl was examined for her severe hypotonia, developmental delay, and mild dysmorphic appearance. Clinical features include broad forehead, hypertelorism, laterally extended eyebrows, long eyelashes, a depressed nasal root, bifid nasal tip, long philtrum, thin lips, posteriorly rotated ears, short neck, partial syndactyly of the right hand (fingers 3, 4) , and partial syndactyly of the right foot (toes 2, 3). After examination, the final karyo...
Source: Molecular Syndromology - June 9, 2020 Category: Molecular Biology Source Type: research

Intrafamilial Variability in < b > < i > LPIN1 < /i > < /b > -Related Rhabdomyolysis
This report expands the phenotypic spectrum ofLPIN1-related rhabdomyolysis, illustrating high intrafamilial variability.Mol Syndromol 2020;11:153-156 (Source: Molecular Syndromology)
Source: Molecular Syndromology - May 26, 2020 Category: Molecular Biology Source Type: research

How Many Genes Does It Take?
Mol Syndromol 2020;11:59-61 (Source: Molecular Syndromology)
Source: Molecular Syndromology - April 21, 2020 Category: Molecular Biology Source Type: research

Renpenning Syndrome in a Turkish Patient: de novo Variant c.607C > T in < b > < i > PACS1 < /i > < /b > and Hypogammaglobulinemia Phenotype
We report a Turkish child with a novel pathogenic variant inPQBP1 and a likely pathogenic variant in thePACS1 gene presenting with growth restriction, microcephaly, ID, micropenis, bilateral iris coloboma, and hypogammaglobulinemia. Cytogenetic investigations, including a high-resolution-banded karyotype, were normal. Clinical exome sequencing was performed. We found the novelPQBP1 variant, c.640C>T; p.(Arg214Trp), and the knownPACS1 variant, c.607C>T; p.(Arg203Trp), in the proband. The patient's hypogammaglobulinemia did not respond to treatment. This condition was detected for the first time in a patient with Renpe...
Source: Molecular Syndromology - April 16, 2020 Category: Molecular Biology Source Type: research

Proximal Deletion 12q with a New Insight to Growth Retardation
Proximal deletion of the long arm of chromosome 12 is a rare chromosomal abnormality described in about 20 patients. Known deletions span the region from 12q11 to 12q13 and include the genesYAF2,AMIGO2, andNELL2. These are suggested as candidate genes for the key phenotypic features such as growth and psychomotor retardation. Here, we present a case with a 3.1-Mb interstitial deletion at 12q12q13.11. The clinical observations of our patient overlap with the major common findings for published cases. The deletion detected in our patient does not involve the previously suggested candidate genesYAF2 andAMIGO2. We draw a corre...
Source: Molecular Syndromology - April 9, 2020 Category: Molecular Biology Source Type: research

Seizures and Cardiomyopathy in a Patient with Pallister-Killian Syndrome due to Hexasomy 12p Mosaicism
We report a 10 year follow-up on a girl with 2 copies of isochromosome consisting of the short arm of chromosome 12, who has craniofacial features seen in PKS, such as sparse hair with an unusual pattern, sparse eyebrows, lacrimal duct stenosis, submucous cleft palate, Pallister lip (a relatively long philtrum continuing into the vermillion border of the upper lip), narrow palate, and wide alveolar ridges. She also has other abnormalities, including unilateral renal dysgenesis, rectovaginal fistula, pre-axial polydactyly of the right hand, severe global developmental delay, and hypotonia as well as some features suggestive...
Source: Molecular Syndromology - April 9, 2020 Category: Molecular Biology Source Type: research

22q13 Microduplication Syndrome in Siblings with Mild Clinical Phenotype: Broadening the Clinical and Behavioral Spectrum
Distal duplication 22q (22q13.3qter) is a rare condition with only 24 cases described so far. Parental balanced reciprocal translocations and pericentric inversions involving chromosome 22 predispose to the conception of an unbalanced offspring and are more frequently reported than de novo events. The clinical phenotype of patients is highly variable and does not necessarily correlate with the extent of the duplicated segment. Short stature, microcephaly, hypertelorism, cleft lip or palate, low-set ears, and intellectual disability seem to be the most consistent features. Familial reoccurrence is extremely rarely reported....
Source: Molecular Syndromology - April 3, 2020 Category: Molecular Biology Source Type: research

A Recurrent Variant in MAGEL2 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 2, 2019 Category: Molecular Biology Source Type: research

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 2, 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 1, 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 6, 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 6, 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