scholarly journals Targeted gene capture and massively parallel sequencing identify TMC1 as the causative gene in a six-generation Chinese family with autosomal dominant hearing loss

2015 ◽  
Vol 167 (10) ◽  
pp. 2357-2365 ◽  
Author(s):  
Xue Gao ◽  
Sha-Sha Huang ◽  
Yong-Yi Yuan ◽  
Guo-Jian Wang ◽  
Jin-Cao Xu ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Autosomal Dominant ◽  
Massively Parallel Sequencing ◽  
Massively Parallel ◽  
Chinese Family ◽  
Causative Gene ◽  
Parallel Sequencing ◽  
Gene Capture

scholarly journals USH2A mutations identified by massively parallel sequencing in 3 children with sensorineural hearing loss

2019 ◽  
Vol 62 (3) ◽  
pp. 218-223
Author(s):  
Mayuri Okami ◽  
Momoko Tsukahara ◽  
Kenji Okami ◽  
Masahiro Iida ◽  
Kazumi Takahashi ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Sensorineural Hearing Loss ◽  
Massively Parallel Sequencing ◽  
Sensorineural Hearing ◽  
Massively Parallel ◽  
Parallel Sequencing

scholarly journals Massively Parallel Sequencing for Rare Genetic Disorders: Potential and Pitfalls

2021 ◽  
Vol 11 ◽  
Author(s):  
Aideen M. McInerney-Leo ◽  
Emma L. Duncan
Keyword(s):  
Linkage Analysis ◽  
Positional Cloning ◽  
De Novo ◽  
Massively Parallel Sequencing ◽  
Diagnostic Yield ◽  
Massively Parallel ◽  
Disease Genes ◽  
Causative Gene ◽  
Parallel Sequencing ◽  
Diagnostic Uncertainty

There have been two major eras in the history of gene discovery. The first was the era of linkage analysis, with approximately 1,300 disease-related genes identified by positional cloning by the turn of the millennium. The second era has been powered by two major breakthroughs: the publication of the human genome and the development of massively parallel sequencing (MPS). MPS has greatly accelerated disease gene identification, such that disease genes that would have taken years to map previously can now be determined in a matter of weeks. Additionally, the number of affected families needed to map a causative gene and the size of such families have fallen: de novo mutations, previously intractable by linkage analysis, can be identified through sequencing of the parent–child trio, and genes for recessive disease can be identified through MPS even of a single affected individual. MPS technologies include whole exome sequencing (WES), whole genome sequencing (WGS), and panel sequencing, each with their strengths. While WES has been responsible for most gene discoveries through MPS, WGS is superior in detecting copy number variants, chromosomal rearrangements, and repeat-rich regions. Panels are commonly used for diagnostic purposes as they are extremely cost-effective and generate manageable quantities of data, with no risk of unexpected findings. However, in instances of diagnostic uncertainty, it can be challenging to choose the right panel, and in these circumstances WES has a higher diagnostic yield. MPS has ethical, social, and legal implications, many of which are common to genetic testing generally but amplified due to the magnitude of data (e.g., relationship misattribution, identification of variants of uncertain significance, and genetic discrimination); others are unique to WES and WGS technologies (e.g., incidental or secondary findings). Nonetheless, MPS is rapidly translating into clinical practice as an extremely useful part of the clinical armamentarium.

Non-ocular Stickler Syndrome With a Novel Mutation in COL11A2 Diagnosed by Massively Parallel Sequencing in Japanese Hearing Loss Patients

2015 ◽  
Vol 124 (1_suppl) ◽  
pp. 111S-117S ◽  
Author(s):  
Yoh-ichiro Iwasa ◽  
Hideaki Moteki ◽  
Mitsuru Hattori ◽  
Ririko Sato ◽  
Shin-ya Nishio ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Clinical Symptoms ◽  
Massively Parallel Sequencing ◽  
Novel Mutation ◽  
Genetic Diagnosis ◽  
Analysis Data ◽  
Massively Parallel ◽  
Stickler Syndrome ◽  
Parallel Sequencing ◽  
First Case

Objectives: This study aims to document the clinical features of patients with COL11A2 mutations and to describe the usefulness of massively parallel sequencing. Methods: One thousand one hundred twenty (1120) Japanese hearing loss patients from 53 ENT departments nationwide participated in this study. Massively parallel sequencing of 63 genes implicated in hearing loss was performed to identify the genetic causes in the Japanese hearing loss patients. Results: A novel mutation in COL11A2 (c.3937_3948delCCCCCAGGGCCA) was detected in an affected family, and it was segregated in all hearing loss individuals. The clinical findings of this family were compatible with non-ocular Stickler syndrome. Orofacial features of mid-facial hypoplasia and slowly progressive mild to moderate hearing loss were also presented. Audiological examinations showed favorable auditory performance with hearing aid(s). Conclusion: This is the first case report of the genetic diagnosis of a non-ocular Stickler syndrome family in the Japanese population. We suggest that it is important to take both genetic analysis data and clinical symptoms into consideration to make an accurate diagnosis.

Brief Report of Variants Detected in Hereditary Hearing Loss Cases in Iran over a 3-Year Period

2020 ◽  
Author(s):  
Niloofar BAZAZZADEGAN ◽  
Raheleh VAZEHAN ◽  
Mahsa FADAEE ◽  
Zohreh FATTAHI ◽  
Ayda ABOLHASSANI ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Genetic Testing ◽  
Massively Parallel Sequencing ◽  
Cost Effective ◽  
Massively Parallel ◽  
Parallel Sequencing ◽  
Hereditary Hearing Loss ◽  
Targeted Genomic Enrichment ◽  
Novel Variants ◽  
Autosomal Recessive Pattern

Background: Diagnosis of hereditary hearing loss (HHL) as a heterogeneous disorder is very important especially in countries with high rates of consanguinity where the autosomal recessive pattern of inheritance is prevalent. Techniques such as next-generation sequencing, a comprehensive genetic test using targeted genomic enrichment and massively parallel sequencing (TGE + MPS), have made the diagnosis more cost-effective. The aim of this study was to determine HHL variants with comprehensive genetic testing in our country. of this study was to determine HHL variants with comprehensive genetic testing in our country. Methods: Fifty GJB2 negative individuals with HHL were referred to the Kariminejad-Najmabadi Pathology and Genetics Center, Tehran, one of the reference diagnostic genetic laboratories in Iran, during a 3-year period between 2014 and 2017. They were screened with the OtoSCOPE test, the targeted genomic enrichment and massively parallel sequencing (TGE + MPS) platform after a detailed history had been taken along with clinical evaluation. Results: Among 32 out of 50 GJB2 negative patients (64%), 34 known pathogenic and novel variants were detected of which 16 (47%) were novel, identified in 10 genes of which the most prevalent were CDH23, MYO7A and MYO15A. Conclusion: These results provide a foundation from which to make appropriate recommendations for the use of comprehensive genetic testing in the evaluation of Iranian patients with hereditary hearing loss.

Novel Mutations in GRXCR1 at DFNB25 Lead to Progressive Hearing Loss and Dizziness

2015 ◽  
Vol 124 (1_suppl) ◽  
pp. 129S-134S ◽  
Author(s):  
Kentaro Mori ◽  
Ikuyo Miyanohara ◽  
Hideaki Moteki ◽  
Shin-ya Nishio ◽  
Yuichi Kurono ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Massively Parallel Sequencing ◽  
Massively Parallel ◽  
Compound Heterozygous ◽  
Nonsyndromic Hearing Loss ◽  
Novel Mutations ◽  
Progressive Hearing Loss ◽  
Severe Hearing Loss ◽  
Parallel Sequencing ◽  
Targeted Genomic Enrichment

Objective: We identified 2 patients in 1 family who had novel mutations in GRXCR1, which caused progressive hearing loss. Methods: One thousand one hundred twenty Japanese hearing loss patients with sensorineural hearing loss from unrelated families were enrolled in this study. Targeted genomic enrichment with massively parallel sequencing of all known nonsyndromic hearing loss genes was used to identify the genetic causes of hearing loss. Results: In this study, 2 affected individuals with compound heterozygous mutations—c.439C>T (p.R147C) and c.784C>T (p.R262X)—in GRXCR1 were identified. The proband had moderate to severe hearing loss and suffered from dizziness with bilateral canal paralysis. Conclusion: Our cases are the first identified in the Japanese population and are consistent with previously reported cases. The frequency of mutations in GRXCR1 seems to be extremely rare. This study underscores the importance of using comprehensive genetic testing for hearing loss. Furthermore, longitudinal audiologic assessment and precise vestibular testing are necessary for a better understanding of the mechanisms of hearing loss and vestibular dysfunction caused by GRXCR1 mutations.

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