scholarly journals Racial and ethnic disparities in genetic testing for hearing loss: a systematic review and synthesis

2021 ◽  
Author(s):  
Stephanie L. Rouse ◽  
Michelle M. Florentine ◽  
Emily Taketa ◽  
Dylan K. Chan
Keyword(s):  
Hearing Loss ◽  
Genetic Testing ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Single Gene ◽  
Ethnic Disparities ◽  
Multiple Gene ◽  
Whole Exome ◽  
Latino American ◽  
Racial Ethnic

AbstractRacial/ethnic disparities in the diagnostic efficacy of genetic testing for hearing loss have been described. These disparities may relate to differences in variant classification between different racial/ethnic groups, which may, in turn, derive from disparate representation of these groups in the published literature. We sought to quantify racial/ethnic disparities in the published literature on the human genetics of hearing loss. We conducted a search of PubMed for articles describing single-gene, multiple-gene, or whole-exome sequencing for individuals with sensorineural hearing loss. Data on the included subjects, including race/ethnicity and/or region of origin, a number of subjects tested, and method of testing, were extracted. 1355 populations representing 311,092 subjects from 1165 studies were included. Overall, subjects of European and Asian ancestry were equivalently represented, but those of Latino American, African, and indigenous North American ancestry were significantly underrepresented; over 96% of all subjects in the published literature were European or Asian. Within populations, the majority of subjects derived from a small subset of countries. The observed disparity was greater for multiple-gene and whole-exome sequencing than for single-gene sequencing. These findings illustrate the large disparity in the published literature on the genetics of hearing loss, and demonstrate the need for increased representation of Latino American, African, and indigenous North American populations.

scholarly journals Racial and Ethnic Disparities in Genetic Testing for Hearing Loss: a Systematic Review and Synthesis

2021 ◽  
Author(s):  
Stephanie L Rouse ◽  
Michelle M Florentine ◽  
Emily Taketa ◽  
Dylan K Chan
Keyword(s):  
Hearing Loss ◽  
Native American ◽  
Genetic Testing ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Single Gene ◽  
Ethnic Disparities ◽  
Multiple Gene ◽  
Whole Exome ◽  
Racial Ethnic

Abstract Racial/ethnic disparities in the diagnostic efficacy of genetic testing for hearing loss has been described. These disparities may relate to differences in variant classification between different racial/ethnic groups, which may in turn derive from disparate representation of these groups in the published literature. We sought to quantify racial/ethnic disparities in the published literature on the human genetics of hearing loss. We conducted a search of PubMed for articles describing single-gene, multiple-gene, or whole-exome sequencing for individuals with sensorineural hearing loss. Data on the populations studied, including race/ethnicity and/or region of origin, subjects tested, and method of testing, were extracted. 1,355 unique populations representing 311,092 subjects from 1,165 studies were included. Overall, White and Asian populations and subjects were equivalently represented, but Latinx, Black, and Native American/Hawaiian groups were significantly underrepresented; over 96% of all subjects in the published literature were White or Asian. Within racial/ethnic groups, the majority of subjects derived from a small subset of countries. The observed racial/ethnic disparity was greater for multiple-gene and whole-exome sequencing than for single-gene sequencing. These findings illustrate the large disparity in published literature on the genetics of hearing loss, and demonstrate the need for increased representation of Latinx, Black, and Native American populations.

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.

scholarly journals Whole-exome sequencing associates novel CSMD1 gene mutations with familial Parkinson disease

2017 ◽  
Vol 3 (5) ◽  
pp. e177 ◽  
Author(s):  
Javier Ruiz-Martínez ◽  
Luis J. Azcona ◽  
Alberto Bergareche ◽  
Jose F. Martí-Massó ◽  
Coro Paisán-Ruiz
Keyword(s):  
Parkinson Disease ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Genome Wide Association Study ◽  
Single Gene ◽  
Gene Mutations ◽  
Complement Control Protein ◽  
Genome Wide ◽  
Whole Exome ◽  
A Genome

Objective:Despite the enormous advancements made in deciphering the genetic architecture of Parkinson disease (PD), the majority of PD is idiopathic, with single gene mutations explaining only a small proportion of the cases.Methods:In this study, we clinically evaluated 2 unrelated Spanish families diagnosed with PD, in which known PD genes were previously excluded, and performed whole-exome sequencing analyses in affected individuals for disease gene identification.Results:Patients were diagnosed with typical PD without relevant distinctive symptoms. Two different novel mutations were identified in the CSMD1 gene. The CSMD1 gene, which encodes a complement control protein that is known to participate in the complement activation and inflammation in the developing CNS, was previously shown to be associated with the risk of PD in a genome-wide association study.Conclusions:We conclude that the CSMD1 mutations identified in this study might be responsible for the PD phenotype observed in our examined patients. This, along with previous reported studies, may suggest the complement pathway as an important therapeutic target for PD and other neurodegenerative diseases.

scholarly journals Whole-Exome Sequencing to Decipher the Genetic Heterogeneity of Hearing Loss in a Chinese Family with Deaf by Deaf Mating

PLoS ONE ◽  
2014 ◽  
Vol 9 (10) ◽  
pp. e109178 ◽  
Author(s):  
Jie Qing ◽  
Denise Yan ◽  
Yuan Zhou ◽  
Qiong Liu ◽  
Weijing Wu ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Genetic Heterogeneity ◽  
Chinese Family ◽  
Whole Exome

Diversity of the genes involved in Algerian families with hearing loss identified by whole exome sequencing

2018 ◽  
Vol 44 ◽  
pp. S95
Author(s):  
M. Dahmani ◽  
F. Ammar Khodja ◽  
C. Bonnet ◽  
D. Djennaoui ◽  
S. Ouhab ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Whole Exome

Abstract 16468: Results of Research Genetic Testing in Pediatric Cardiomyopathy Patients Justify Broader Clinical Genetic Testing

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Stephanie M Ware ◽  
Steven E Lipshultz ◽  
Steven D Colan ◽  
Ling Shi ◽  
Charles E Canter ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Family History ◽  
Risk Stratification ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Clinical Genetic ◽  
Clinical Genetic Testing ◽  
Whole Exome ◽  
Pediatric Cardiomyopathy ◽  
History Of

Introduction: Pediatric cardiomyopathies are genetically heterogeneous diseases with high risk of death or cardiac transplant. Despite progress in identifying causes, the majority of cases remain idiopathic. Currrently, genetic testing is not performed in all children with cardiomyopathy. Gene identification leads to better individual risk stratification and has the potential to stimulate the development of therapies based on the underlying mutation. The aim of this study is to identify genetic mutations in pediatric cardiomyopathy patients using whole exome sequencing. Hypothesis: Sarcomeric mutations are under-diagnosed causes of all forms of cardiomyopathy in children. Methods: Probands with cardiomyopathy were recruited from 11 institutions. Results of clinical genetic testing prior to enrollment were collected. Whole exome sequencing was performed and mutations were identified in 35 genes currently available on clinical genetic testing panels. Results: The initial 154 probands subjected to exome included 78 patients with DCM, 43 with HCM, 14 with RCM, and 19 with LVNC, mixed, or unknown types. Familial disease was present in 38% and the remainder were idiopathic. Twenty-seven percent had positive clinical genetic testing prior to enrollment. Exome testing identified mutations in 38 subjects who had not had clinical testing, increasing the cohort positive testing rate to 55% (DCM, 34.6%; HCM, 74.4%; RCM, 71.4%). Forty-five percent of subjects with no family history of disease had an identifiable mutation. Conclusions: Pediatric cardiomyopathy patients have a high incidence of mutations that can be identified by clinically available genetic testing. Lack of a family history of cardiomyopathy was not predictive of normal genetic testing. These results support the broader use of genetic testing in pediatric patients with all functional phenotypes of cardiomyopathy to identify disease causation allowing better family risk stratification.

Whole Exome Sequencing of Six Chinese Families With Hereditary Non-Syndromic Hearing Loss: A Genetic Etiology Study

2020 ◽  
Author(s):  
Pengfei Liang ◽  
Fengping Chen ◽  
Shujuan Wang ◽  
Qiong Li ◽  
Wei Li ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Sanger Sequencing ◽  
Large Scale ◽  
Autosomal Recessive ◽  
Autosomal Recessive Inheritance ◽  
Chinese Families ◽  
Whole Exome ◽  
Syndromic Hearing Loss

Abstract Background: Hereditary non-syndromic hearing loss (NSHL) has a high genetic heterogeneity with >152 genes identified as associated molecular causes. The present study aimed to detect the possible damaging variants of the deaf probands from six unrelated Chinese families.Methods: After excluding the mutations in the most common genes, GJB2 and SLC26A4, 12 probands with prelingual deafness and autosomal recessive inheritance were evaluated by whole-exome sequencing (WES). All the candidate variants were verified by Sanger sequencing in all patients and their parents.Results: Biallelic mutations were identified in all deaf patients. Among these six families, 10 potentially causative mutations, including 3 reported and 7 novel mutations, in 3 different deafness-associated autosomal recessive (DFNB) genes (MYO15A, COL11A2, and CDH23) were identified. The mutations in MYO15A were frequent with 7/10 candidate variants. Sanger sequencing confirmed that these mutations segregated with the hearing loss of each family.Conclusions: Next-generation sequencing (NGS) approach becomes more cost-effective and efficient when analyzing large-scale genes compared to the conventional polymerase chain reaction-based Sanger sequencing, which is often used to screen common deafness-related genes. The current findings further extend the mutation spectrum of hearing loss in the Chinese population, which has a positive significance for genetic counseling.

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