scholarly journals Diagnostic Exome Sequencing and Tailored Bioinformatics of the Parents of a Deceased Child with Cobalamin Deficiency Suggests Digenic Inheritance of the MTR and LMBRD1 Genes

2014 ◽  
Author(s):  
Kelly D. Farwell Gonzalez ◽  
Xiang Li ◽  
Hsiao-Mei Lu ◽  
Hong Lu ◽  
Joan E. Pellegrino ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Cobalamin Deficiency ◽  
Digenic Inheritance ◽  
Deceased Child

scholarly journals Putative Digenic GJBI2/MYO7A Inheritance of Hearing Loss Detected in a Patient with 48, XXYY Klinefelter Syndrome

2020 ◽  
Author(s):  
Tian-tian Qin ◽  
Qin Zhang ◽  
Wen-mu Hu ◽  
Muhammad Usman Janjua ◽  
Qin Long ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Sex Chromosome ◽  
Chromosome Abnormality ◽  
Klinefelter Syndrome ◽  
Compound Heterozygous ◽  
Pathogenic Variants ◽  
Digenic Inheritance ◽  
Whole Exome

Abstract Background: 48, XXYY Klinefelter syndrome is a rare sex chromosome abnormality. Nonsyndromic hearing loss (NSHL) is the most frequent hereditary type of hearing impairment. There has been no report of NSHL combined with 48XXYY. The purpose of this study was to explore the underlying genetic cause in a three-generation family affected by NSHL. The proband had concomitant NSHL and 48, XXYY syndrome. The whole-exome sequencing was performed in the proband. The candidate pathogenic variants identified by whole-exome sequencing were then confirmed by Sanger sequencing and segregation analysis.Results: The proband was identified to be compound heterozygous for c.109G>A (p.V37I) variant in the GJB2 gene and additional heterozygous for the c.1039C>A (p.L347I) variants in the MYO7A gene. His mother had normal hearing and did not have any form of variant. His father and uncle, both had NSHL, were digenic compound heterozygote for the GJB2 p.V37I and MYO7A p.L347I variants, thus suggesting a possible GJB2/MYO7A digenic inheritance of NSHL in this family consist with the clinical phenotype.Conclusions: Our findings reported a putative GJB2/MYO7A digenic inheritance form of hearing loss, which expands the mutation spectrum of NSHL. This is also the first report of concomitant NSHL and 48, XXYY syndrome.

scholarly journals Frameshift variant in MITF gene in a large family with Waardenburg syndrome type II and a co-segregation of a C2orf74 variant

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0246607
Author(s):  
Maan Abdullah Albarry ◽  
Muhammad Latif ◽  
Ahdab Qasem Alreheli ◽  
Mohammed A. Awadh ◽  
Ahmad M. Almatrafi ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Large Family ◽  
Snp Genotyping ◽  
Whole Genome ◽  
Waardenburg Syndrome ◽  
Single Nucleotide ◽  
Digenic Inheritance ◽  
Whole Exome

Waardenburg syndrome (WS) is a hereditary disorder affecting the auditory system and pigmentation of hair, eyes, and skin. Different variants of the disease exist with the involvement of mutation in six genes. The aim of the study is to identify the genetic defects underlying Waardenburg syndrome in a large family with multiple affected individuals. Here, in this study, we recruited a large family with eleven affected individuals segregating WS type 2. We performed whole genome SNP genotyping, whole exome sequencing and segregation analysis using Sanger approach. Whole genome SNP genotyping, whole exome sequencing followed by Sanger validation of variants of interest identified a novel single nucleotide deletion mutation (c.965delA) in the MITF gene. Moreover, a rare heterozygous, missense damaging variant (c.101T>G; p.Val34Gly) in the C2orf74 has also been identified. The C2orf74 is an uncharacterized gene present in the linked region detected by DominantMapper. Variants in MITF and C2orf74 follows autosomal dominant segregation with the phenotype, however, the variant in C2orf74 is incompletely penetrant. We proposed a digenic inheritance of variants as an underlying cause of WS2 in this family.

scholarly journals Putative Digenic GJB2/MYO7A Inheritance of Hearing Loss Detected in a Patient with 48,XXYY Klinefelter Syndrome

2021 ◽  
pp. 1-7
Author(s):  
Qin Zhang ◽  
Tiantian Qin ◽  
Wenmu Hu ◽  
Muhammad Usman Janjua ◽  
Ping Jin
Keyword(s):  
Hearing Loss ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Klinefelter Syndrome ◽  
Pathogenic Variants ◽  
Digenic Inheritance ◽  
Whole Exome ◽  
Bioinformatics Software ◽  
Pedigree Verification ◽  
Hereditary Hearing Impairment

<b><i>Objectives:</i></b> Nonsyndromic hearing loss (NSHL) is the most frequent type of hereditary hearing impairment. Here, we explored the underlying genetic cause of NSHL in a three-generation family using whole-exome sequencing. The proband had concomitant NSHL and rare 48,XXYY Klinefelter syndrome. <b><i>Material and Methods:</i></b> Genomic DNA was extracted from the peripheral blood of the proband and their family members. Sanger sequencing and pedigree verification were performed on the pathogenic variants filtered by whole-exome sequencing. The function of the variants was analyzed using bioinformatics software. <b><i>Results:</i></b> The proband was digenic heterozygous for p.V37I in the <i>GJB2</i> gene and p.L347I in the <i>MYO7A</i> gene. The proband’s mother had normal hearing and did not have any variant. The proband’s father and uncle both had NSHL and were compound for the <i>GJB2</i> p.V37I and <i>MYO7A</i> p.L347I variants, thus indicating a possible <i>GJB2/MYO7A</i> digenic inheritance of NSHL. 48,XXYY Klinefelter syndrome was discovered in the proband after the karyotype analysis, while his parents both had normal karyotypes. <b><i>Conclusions:</i></b> Our findings reported a putative <i>GJB2/MYO7A</i> digenic inheritance form of hearing loss, expanding the genotype and phenotype spectrum of NSHL. In addition, this is the first report of concomitant NSHL and 48,XXYY syndrome.

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

Identification of Novel Germline and Tumor-Specific Nucleotide Variants and Copy Number Variation in Clival Chordomas by Exome Sequencing

2015 ◽  
Vol 76 (S 01) ◽  
Author(s):  
Georgios Zenonos ◽  
Peter Howard ◽  
Maureen Lyons-Weiler ◽  
Wang Eric ◽  
William LaFambroise ◽  
...  
Keyword(s):  
Copy Number Variation ◽  
Exome Sequencing ◽  
Copy Number ◽  
Number Variation ◽  
Specific Nucleotide
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