Warburg Micro Syndrome 1 due to Segmental Paternal Uniparental Isodisomy of Chromosome 2 Detected by Whole-Exome Sequencing and Homozygosity Mapping

2020 ◽  
Vol 160 (6) ◽  
pp. 309-315
Author(s):  
Abdullah Sezer ◽  
Gülsüm Kayhan ◽  
Altuğ Koç ◽  
Mehmet A. Ergün ◽  
Ferda E. Perçin
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Uniparental Disomy ◽  
Homozygosity Mapping ◽  
Spastic Diplegia ◽  
Chromosome 2 ◽  
Whole Exome ◽  
Uniparental Isodisomy ◽  
Mapping Analysis ◽  
Warburg Micro Syndrome

Warburg micro syndrome (WARBM) is a rare autosomal recessive disorder characterized by microcephaly, cortical dysplasia, intellectual disability, ocular abnormalities, spastic diplegia, and microgenitalia. WARBM has 4 subtypes arising from pathogenic variants in 4 genes (RAB18, RAB3GAP1, RAB3GAP2, and TBC1D20). Here, we report on a patient with a homozygous pathogenic c.665delC (p.Pro222HisfsTer30) variant in the RAB3GAP1 gene identified by whole-exome sequencing (WES) analyses. Only his father was a heterozygous carrier, and homozygosity mapping analysis of the WES data revealed large loss-of-heterozygosity regions in both arms of chromosome 2, interpreted as uniparental isodisomy. This uniparental disomy pattern could be due to paternal meiosis I nondisjunction because of the preserved heterozygosity in the pericentromeric region. This report provides novel insights, including a rare form of UPD, usage of homozygosity mapping analysis for the evaluation of isodisomy, and the first reported case of WARBM1 as a result of uniparental isodisomy.

scholarly journals Whole exome sequencing in a patient with uniparental disomy of chromosome 2 and a complex phenotype

2012 ◽  
Vol 84 (3) ◽  
pp. 213-222 ◽  
Author(s):  
H Carmichael ◽  
Y Shen ◽  
TT Nguyen ◽  
JN Hirschhorn ◽  
A Dauber
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Uniparental Disomy ◽  
Chromosome 2 ◽  
Complex Phenotype ◽  
Whole Exome

scholarly journals One test for all: whole exome sequencing significantly improves the diagnostic yield in growth retarded patients referred for molecular testing for Silver–Russell syndrome

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Robert Meyer ◽  
Matthias Begemann ◽  
Christian Thomas Hübner ◽  
Daniela Dey ◽  
Alma Kuechler ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Diagnostic Yield ◽  
Uniparental Disomy ◽  
Molecular Testing ◽  
Main Body ◽  
Comprehensive Overview ◽  
Maternal Uniparental Disomy ◽  
Whole Exome ◽  
Silver Russell Syndrome

Abstract Background Silver-Russell syndrome (SRS) is an imprinting disorder which is characterised by severe primordial growth retardation, relative macrocephaly and a typical facial gestalt. The clinical heterogeneity of SRS is reflected by a broad spectrum of molecular changes with hypomethylation in 11p15 and maternal uniparental disomy of chromosome 7 (upd(7)mat) as the most frequent findings. Monogenetic causes are rare, but a clinical overlap with numerous other disorders has been reported. However, a comprehensive overview on the contribution of mutations in differential diagnostic genes to phenotypes reminiscent to SRS is missing due to the lack of appropriate tests. With the implementation of next generation sequencing (NGS) tools this limitation can now be circumvented. Main body We analysed 75 patients referred for molecular testing for SRS by a NGS-based multigene panel, whole exome sequencing (WES), and trio-based WES. In 21/75 patients a disease-causing variant could be identified among them variants in known SRS genes (IGF2, PLAG1, HMGA2). Several patients carried variants in genes which have not yet been considered as differential diagnoses of SRS. Conclusions WES approaches significantly increase the diagnostic yield in patients referred for SRS testing. Several of the identified monogenetic disorders have a major impact on clinical management and genetic counseling.

scholarly journals Exome sequencing identified a novelde novo OPA1mutation in a consanguineous family presenting with optic atrophy

2016 ◽  
Vol 98 ◽  
Author(s):  
LIOR COHEN ◽  
SHAY TZUR ◽  
NITZA GOLDENBERG-COHEN ◽  
CONCETTA BORMANS ◽  
DORON M. BEHAR ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Optic Neuropathy ◽  
Optic Atrophy ◽  
De Novo ◽  
Extended Family ◽  
Homozygosity Mapping ◽  
Visual Field Defects ◽  
Whole Exome ◽  
Hereditary Optic Neuropathy

SummaryInherited optic neuropathies are a heterogeneous group of disorders characterized by mild to severe visual loss, colour vision deficit, central or paracentral visual field defects and optic disc pallor. Optic atrophies can be classified into isolated or non-syndromic and syndromic forms. While multiple modes of inheritance have been reported, autosomal dominant optic atrophy and mitochondrial inherited Leber's hereditary optic neuropathy are the most common forms. Optic atrophy type 1, caused by mutations in theOPA1gene is believed to be the most common hereditary optic neuropathy, and most patients inherit a mutation from an affected parent. In this study we used whole-exome sequencing to investigate the genetic aetiology in a patient affected with isolated optic atrophy. Since the proband was the only affected individual in his extended family, and was a product of consanguineous marriage, homozygosity mapping followed by whole-exome sequencing were pursued. Exome results identified a novelde novo OPA1mutation in the proband. We conclude, that thoughde novo OPA1mutations are uncommon, testing of common optic atrophy-associated genes such as mitochondrial mutations andOPA1gene sequencing should be performed first in single individuals presenting with optic neuropathy, even when dominant inheritance is not apparent.

Homozygosity mapping and whole exome sequencing provide exact diagnosis of Cohen syndrome in a Saudi family

2020 ◽  
Vol 42 (8) ◽  
pp. 587-593
Author(s):  
Jamil A. Hashmi ◽  
Fatima Fadhli ◽  
Ahmed Almatrafi ◽  
Sibtain Afzal ◽  
Khushnooda Ramzan ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Homozygosity Mapping ◽  
Cohen Syndrome ◽  
Whole Exome ◽  
Saudi Family ◽  
Exact Diagnosis

scholarly journals Homozygosity Mapping and Whole Exome Sequencing Reveal a Novel Homozygous COL18A1 Mutation Causing Knobloch Syndrome

PLoS ONE ◽  
2014 ◽  
Vol 9 (11) ◽  
pp. e112747 ◽  
Author(s):  
Alireza Haghighi ◽  
Amit Tiwari ◽  
Niloofar Piri ◽  
Gudrun Nürnberg ◽  
Nasrollah Saleh-Gohari ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Homozygosity Mapping ◽  
Knobloch Syndrome ◽  
Whole Exome

scholarly journals Two novel Warburg micro syndrome 1 cases caused by pathogenic variants in RAB3GAP1

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Omid Alavi ◽  
Hossein Jafari Khamirani ◽  
Sina Zoghi ◽  
Afrooz Feili ◽  
Seyed Alireza Dastgheib ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Corpus Callosum ◽  
Exome Sequencing ◽  
Developmental Delay ◽  
Whole Exome Sequencing ◽  
Drug Resistant ◽  
Pathogenic Variants ◽  
Whole Exome ◽  
Warburg Micro Syndrome ◽  
Craniofacial Features

AbstractIn this study, we detected a novel pathogenic variant and a previously reported variant in RAB3GAP1 by whole-exome sequencing (NM_001172435.2: c.1552C>T, p.Gln518*; c.1471C>T, p.Arg491*). The first patient is a 3-year-old girl who presented with bilateral congenital cataracts, developmental delay, abnormal craniofacial features, drug-resistant constipation, and corpus callosum hypoplasia. The proband of the second family is a 13-year-old boy who suffers from developmental delay, quadriplegia, intellectual disability, abnormal craniofacial features, and corpus callosum hypoplasia.

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