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.

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 Whole exome sequencing identifies TRIOBP pathogenic variants as a cause of post-lingual bilateral moderate-to-severe sensorineural hearing loss

2017 ◽  
Vol 18 (1) ◽  
Author(s):  
Agnieszka Pollak ◽  
Urszula Lechowicz ◽  
Victor Abel Murcia Pieńkowski ◽  
Piotr Stawiński ◽  
Joanna Kosińska ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Sensorineural Hearing Loss ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Sensorineural Hearing ◽  
Pathogenic Variants ◽  
Whole Exome

scholarly journals Whole-exome sequencing with targeted analysis and epilepsy after acute symptomatic neonatal seizures

2021 ◽  
Author(s):  
Adam L. Numis ◽  
Gilberto da Gente ◽  
Elliott H. Sherr ◽  
Hannah C. Glass
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
De Novo ◽  
List Type ◽  
Sequencing Analysis ◽  
Neonatal Seizures ◽  
Pathogenic Variants ◽  
Targeted Analysis ◽  
Whole Exome ◽  
Epilepsy Gene

Abstract Background The contribution of pathogenic gene variants with development of epilepsy after acute symptomatic neonatal seizures is not known. Methods Case–control study of 20 trios in children with a history of acute symptomatic neonatal seizures: 10 with and 10 without post-neonatal epilepsy. We performed whole-exome sequencing (WES) and identified pathogenic de novo, transmitted, and non-transmitted variants from established and candidate epilepsy association genes and correlated prevalence of these variants with epilepsy outcomes. We performed a sensitivity analysis with genes associated with coronary artery disease (CAD). We analyzed variants throughout the exome to evaluate for differential enrichment of functional properties using exploratory KEGG searches. Results Querying 200 established and candidate epilepsy genes, pathogenic variants were identified in 5 children with post-neonatal epilepsy yet in only 1 child without subsequent epilepsy. There was no difference in the number of trios with non-transmitted pathogenic variants in epilepsy or CAD genes. An exploratory KEGG analysis demonstrated a relative enrichment in cell death pathways in children without subsequent epilepsy. Conclusions In this pilot study, children with epilepsy after acute symptomatic neonatal seizures had a higher prevalence of coding variants with a targeted epilepsy gene sequencing analysis compared to those patients without subsequent epilepsy. Impact We performed whole-exome sequencing (WES) in 20 trios, including 10 children with epilepsy and 10 without epilepsy, both after acute symptomatic neonatal seizures. Children with post-neonatal epilepsy had a higher burden of pathogenic variants in epilepsy-associated genes compared to those without post-neonatal epilepsy. Future studies evaluating this association may lead to a better understanding of the risk of epilepsy after acute symptomatic neonatal seizures and elucidate molecular pathways that are dysregulated after brain injury and implicated in epileptogenesis.

scholarly journals Novel MYO15A variants are associated with hearing loss in the two Iranian pedigrees

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Somayeh Khatami ◽  
Masomeh Askari ◽  
Fatemeh Bahreini ◽  
Morteza Hashemzadeh-Chaleshtori ◽  
Saeed Hematian ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Genetic Diagnosis ◽  
Clinical Genetic ◽  
Large Size ◽  
Whole Exome ◽  
Novel Variants ◽  
Syndromic Hearing Loss ◽  
Traditional Approaches

Abstract Background Clinical genetic diagnosis of non-syndromic hearing loss (NSHL) is quite challenging. With regard to its high heterogeneity as well as large size of some genes, it is also really difficult to detect causative mutations using traditional approaches. One of the recent technologies called whole-exome sequencing (WES) has been thus developed in this domain to remove the limitations of conventional methods. Methods This study was a report on a research study of two unrelated pedigrees with multiple affected cases of hearing loss (HL). Accordingly, clinical evaluations and genetic analysis were performed in both families. Results The results of WES data analysis to uncover autosomal recessive non-syndromic hearing loss (ARNSHL) disease-causing variants was reported in the present study. Initial analysis identified two novel variants of MYO15A i.e. c.T6442A:p.W2148R and c.10504dupT:p.C3502Lfs*15 correspondingly which were later confirmed by Sanger validations and segregation analyses. According to online prediction tools, both identified variants seemed to have damaging effects. Conclusion In this study, whole exome sequencing were used as a first approach strategy to identify the two novel variants in MYO15A in two Iranian families with ARNSHL.

RHOBTB2 p.Arg511Trp Mutation in Early Infantile Epileptic Encephalopathy-64: Review and Case Report

2021 ◽  
Author(s):  
J Fonseca ◽  
C Melo ◽  
C Ferreira ◽  
M Sampaio ◽  
R Sousa ◽  
...  
Keyword(s):  
Case Report ◽  
Intellectual Disability ◽  
Status Epilepticus ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Epileptic Encephalopathy ◽  
Btb Domain ◽  
Pathogenic Variants ◽  
Severe Intellectual Disability ◽  
Whole Exome

AbstractEarly infantile epileptic encephalopathy-64 (EIEE 64), also called RHOBTB2-related developmental and epileptic encephalopathy (DEE), is caused by heterozygous pathogenic variants (EIEE 64; MIM#618004) in the Rho-related BTB domain-containing protein 2 (RHOBTB2) gene. To date, only 13 cases with RHOBTB2-related DEE have been reported. We add to the literature the 14th case of EIEE 64, identified by whole exome sequencing, caused by a heterozygous pathogenic variant in RHOBTB2 (c.1531C > T), p.Arg511Trp. This additional case supports the main features of RHOBTB2-related DEE: infantile-onset seizures, severe intellectual disability, impaired motor functions, postnatal microcephaly, recurrent status epilepticus, and hemiparesis after seizures.

scholarly journals Novel pathogenic variants and genes for myopathies identified by whole exome sequencing

2015 ◽  
Vol 3 (4) ◽  
pp. 283-301 ◽  
Author(s):  
Jesse M. Hunter ◽  
Mary Ellen Ahearn ◽  
Christopher D. Balak ◽  
Winnie S. Liang ◽  
Ahmet Kurdoglu ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Pathogenic Variants ◽  
Whole Exome
Sign in / Sign up

Export Citation Format

Share Document