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) likely ...
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 family...
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
