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

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 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.

Whole exome sequencing resolves complex phenotype and identifies CC2D2A mutations underlying non-syndromic rod-cone dystrophy

2018 ◽  
Vol 95 (2) ◽  
pp. 329-333 ◽  
Author(s):  
Cécile Méjécase ◽  
Aurélie Hummel ◽  
Saddek Mohand-Saïd ◽  
Camille Andrieu ◽  
Said El Shamieh ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Cone Dystrophy ◽  
Complex Phenotype ◽  
Whole Exome

scholarly journals Uniparental disomy determined by whole-exome sequencing in a spectrum of rare motoneuron diseases and ataxias

2017 ◽  
Vol 5 (3) ◽  
pp. 280-286 ◽  
Author(s):  
Dana M. Bis ◽  
Rebecca Schüle ◽  
Jennifer Reichbauer ◽  
Matthis Synofzik ◽  
Tim W. Rattay ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Uniparental Disomy ◽  
Whole Exome ◽  
Motoneuron Diseases

scholarly journals Exome sequencing identified mutations in CASK and MYBPC3 as the cause of a complex dilated cardiomyopathy phenotype

2016 ◽  
Vol 98 ◽  
Author(s):  
EYAL REINSTEIN ◽  
SHAY TZUR ◽  
CONCETTA BORMANS ◽  
DORON M. BEHAR
Keyword(s):  
Dilated Cardiomyopathy ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Gene Mutations ◽  
Missense Variant ◽  
Complex Phenotype ◽  
Complex Phenotypes ◽  
Healthy Mother ◽  
Whole Exome ◽  
Hereditary Cardiomyopathy

SummaryWhole-exome sequencing for clinical applications is now an integral part of medical genetics practice. Though most studies are performed in order to establish diagnoses in individuals with rare and clinically unrecognizable disorders, due to the constantly decreasing costs and commercial availability, whole-exome sequencing has gradually become the initial tool to study patients with clinically recognized disorders when more than one gene is responsible for the phenotype or in complex phenotypes, when variants in more than one gene can be the cause for the disease. Here we report a patient presenting with a complex phenotype consisting of severe, adult-onset, dilated cardiomyopathy, hearing loss and developmental delay, in which exome sequencing revealed two genetic variants that are inherited from a healthy mother: a novel missense variant in the CASK gene, mutations in which cause a spectrum of neurocognitive manifestations, and a second variant, in MYBPC3, that is associated with hereditary cardiomyopathy. We conclude that although the potential for co-occurrence of rare diseases is higher when analyzing undefined phenotypes in consanguineous families, it should also be given consideration in the genetic evaluation of complex phenotypes in non-consanguineous families.

scholarly journals Adrenal Insufficiency, Sex Reversal, and Angelman Syndrome due to Uniparental Disomy Unmasking a Mutation in CYP11A1

2018 ◽  
Vol 89 (3) ◽  
pp. 205-210 ◽  
Author(s):  
Ahlee Kim ◽  
Masanobu Fujimoto ◽  
Vivian Hwa ◽  
Philippe Backeljauw ◽  
Andrew Dauber
Keyword(s):  
Adrenal Insufficiency ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Angelman Syndrome ◽  
Uniparental Disomy ◽  
In Vitro Studies ◽  
Recessive Mutation ◽  
Primary Adrenal Insufficiency ◽  
Whole Exome

Background/Aims: Cholesterol side-chain cleavage enzyme (P450scc) deficiency is a rare genetic disorder causing primary adrenal insufficiency with or without a 46,XY disorder of sexual development (DSD). Herein, we report a case of the combination of primary adrenal insufficiency, a DSD (testes with female external genitalia in a setting of a 47,XXY karyotype), and Angelman syndrome. Methods: Comprehensive genetic analyses were performed, including a single nucleotide polymorphism microarray and whole-exome sequencing. In vitro studies were performed to evaluate the pathogenicity of the novel mutation that was identified by whole-exome sequencing. Results: The patient was found to have segmental uniparental disomy (UPD) of chromosome 15 explaining her diagnosis of Angelman syndrome. Whole-exome sequencing further revealed a novel homozygous intronic variant in CYP11A1, the gene encoding P450scc, found within the region of UPD. In vitro studies confirmed that this variant led to decreased efficiency of CYP11A1 splicing. Conclusion: We report the first case of the combination of 2 rare genetic disorders, Angelman syndrome, and P450scc deficiency. After 20 years of diagnostic efforts, significant advances in genetic diagnostic technology allowed us to determine that these 2 disorders originate from a unified genetic etiology, segmental UPD unmasking a novel recessive mutation in CYP11A1.

Whole exome sequencing in congenital pain insensitivity identifies a novel causative intronicNTRK1-mutation due to uniparental disomy

2016 ◽  
Vol 171 (6) ◽  
pp. 875-878 ◽  
Author(s):  
Ingo Kurth ◽  
Manuela Baumgartner ◽  
Maria Schabhüttl ◽  
Cecilia Tomni ◽  
Reinhard Windhager ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Uniparental Disomy ◽  
Whole Exome

Paternal uniparental disomy of chromosome 19 in a pair of monochorionic diamniotic twins with dysmorphic features and developmental delay

2018 ◽  
Vol 55 (12) ◽  
pp. 847-852 ◽  
Author(s):  
Kit San Yeung ◽  
Matthew Sai Pong Ho ◽  
So Lun Lee ◽  
Anita Sik Yau Kan ◽  
Kelvin Yuen Kwong Chan ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Developmental Delay ◽  
Whole Exome Sequencing ◽  
Snp Array ◽  
Uniparental Disomy ◽  
Global Developmental Delay ◽  
Chromosome 19 ◽  
Dysmorphic Features ◽  
Whole Exome ◽  
Paternal Uniparental Disomy

BackgroundWe report here clinical, cytogenetic and molecular data for a pair of monochorionic diamniotic twins with paternal isodisomy for chromosome 19. Both twins presented with dysmorphic features and global developmental delay. This represents, to our knowledge, the first individual human case of paternal uniparental disomy for chromosome 19 (UPD19).MethodsWhole-exome sequencing, together with conventional karyotype and SNP array analysis were performed along with genome-wide DNA methylation array for delineation of the underlying molecular defects.ResultsConventional karyotyping on amniocytes and lymphocytes showed normal karyotypes for both twins. Whole-exome sequencing did not identify any pathogenic sequence variants but >5000 homozygous exonic variants on chromosome 19, suggestive of UPD19. SNP arrays on blood and buccal DNA both showed paternal isodisomy for chromosome 19. Losses of imprinting for known imprinted genes on chromosome 19 were identified, including ZNF331, PEG3, ZIM2 and MIMT1. In addition, imprinting defects were also identified in genes located on other chromosomes, including GPR1-AS, JAKMP1 and NHP2L1.ConclusionImprinting defects are the most likely cause for the dysmorphism and developmental delay in this first report of monozygotic twins with UPD19. However, epigenotype-phenotype correlation will require identification of additional individuals with UPD19 and further molecular analysis.

Whole Exome Sequencing (WES) in Familien mit linksventrikulärer Ausfluβtraktobstruktion (LVOTO)

2014 ◽  
Vol 62 (S 02) ◽  
Author(s):  
M. Hitz ◽  
S. Al-Turki ◽  
A. Schalinski ◽  
U. Bauer ◽  
T. Pickardt ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Whole Exome
Sign in / Sign up

Export Citation Format

Share Document