scholarly journals Genetic Epidemiology and Clinical Features of Hereditary Hearing Impairment in the Taiwanese Population

Genes ◽  
2019 ◽  
Vol 10 (10) ◽  
pp. 772 ◽  
Author(s):  
Wu ◽  
Tsai ◽  
Lin ◽  
Chen ◽  
Lin ◽  
...  
Keyword(s):  
Hearing Impairment ◽  
Clinical Features ◽  
Genetic Epidemiology ◽  
Genetic Diagnosis ◽  
Genetic Mutations ◽  
Taiwanese Population ◽  
The Past ◽  
Genetic Examination ◽  
Hereditary Hearing Impairment ◽  
Generation Sequencing

Hereditary hearing impairment (HHI) is a common but heterogeneous clinical entity caused by mutations in a plethora of deafness genes. Research over the past few decades has shown that the genetic epidemiology of HHI varies significantly across populations. In this study, we used different genetic examination strategies to address the genetic causes of HHI in a large Taiwanese cohort composed of >5000 hearing-impaired families. We also analyzed the clinical features associated with specific genetic mutations. Our results demonstrated that next-generation sequencing-based examination strategies could achieve genetic diagnosis in approximately half of the families. Common deafness-associated genes in the Taiwanese patients assessed, in the order of prevalence, included GJB2, SLC26A4, OTOF, MYO15A, and MTRNR1, which were similar to those found in other populations. However, the Taiwanese patients had some unique mutations in these genes. These findings may have important clinical implications for refining molecular diagnostics, facilitating genetic counseling, and enabling precision medicine for the management of HHI.

scholarly journals The Genetic Diagnosis of Neurodegenerative Diseases and Therapeutic Perspectives

2018 ◽  
Vol 8 (12) ◽  
pp. 222 ◽  
Author(s):  
Julio-César García ◽  
Rosa-Helena Bustos
Keyword(s):  
Neurodegenerative Diseases ◽  
Lower Cost ◽  
Genetic Diagnosis ◽  
Risk Scores ◽  
Genetic Mutations ◽  
Prevention Strategies ◽  
High Incidence ◽  
Near Future ◽  
Generation Sequencing

Genetics has led to a new focus regarding approaches to the most prevalent diseases today. Ascertaining the molecular secrets of neurodegenerative diseases will lead to developing drugs that will change natural history, thereby affecting the quality of life and mortality of patients. The sequencing of candidate genes in patients suffering neurodegenerative pathologies is faster, more accurate, and has a lower cost, thereby enabling algorithms to be proposed regarding the risk of neurodegeneration onset in healthy persons including the year of onset and neurodegeneration severity. Next generation sequencing has resulted in an explosion of articles regarding the diagnosis of neurodegenerative diseases involving exome sequencing or sequencing a whole gene for correlating phenotypical expression with genetic mutations in proteins having key functions. Many of them occur in neuronal glia, which can trigger a proinflammatory effect leading to defective proteins causing sporadic or familial mutations. This article reviews the genetic diagnosis techniques and the importance of bioinformatics in interpreting results from neurodegenerative diseases. Risk scores must be established in the near future regarding diseases with a high incidence in healthy people for defining prevention strategies or an early start for giving drugs in the absence of symptoms.

Siblings with Instability

2016 ◽  
Author(s):  
Richard A. Walsh
Keyword(s):  
Sanger Sequencing ◽  
Genetic Diagnosis ◽  
The Past ◽  
Powerful Approach ◽  
Uncertain Significance ◽  
Widespread Availability ◽  
Gene Panels ◽  
Underlying Pathophysiology ◽  
Generation Sequencing ◽  
Selection Of

Over the past 5 years, there has been a shift in the approach to searching for a genetic diagnosis in familial ataxic syndromes. Whereas in the past, a limited but expensive search through a selection of commercially available genes using Sanger sequencing was performed, there is now widespread availability of gene panels utilizing next-generation sequencing techniques. This is an efficient and powerful approach that may achieve a diagnosis in more than 30% of patients with a familial ataxia that remain undiagnosed. However, accurate phenotyping remains critical to allow interpretation of sequence variants of uncertain significance, to identify biomarkers that may be useful to monitor future therapies, and to assist with the identification of underlying pathophysiology.

scholarly journals Preimplantation Genetic Diagnosis in Hereditary Hearing Impairment

Diagnostics ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 2395
Author(s):  
Hsin-Lin Chen ◽  
Pei-Hsuan Lin ◽  
Yu-Ting Chiang ◽  
Wen-Jie Huang ◽  
Chi-Fang Lin ◽  
...  
Keyword(s):  
Hearing Impairment ◽  
Preimplantation Genetic Diagnosis ◽  
Quantitative Polymerase Chain Reaction ◽  
Genomic Medicine ◽  
Genetic Diagnosis ◽  
Amplification Refractory Mutation System ◽  
Mutation System ◽  
Sensorineural Hearing Impairment ◽  
History Of ◽  
Hereditary Hearing Impairment

Sensorineural hearing impairment is a common sensory deficit in children and more than 50% of these cases are caused by genetic etiologies, that is, hereditary hearing impairment (HHI). Recent advances in genomic medicine have revolutionized the diagnostics of, and counseling for, HHI, including preimplantation genetic diagnosis (PGD), thus providing parents-to-be with better reproductive choices. Over the past decade, we have performed PGD using the amplification refractory mutation system quantitative polymerase chain reaction (ARMS-qPCR) technique in 11 couples with a history of HHI, namely eight with GJB2 variants, one with OTOF variants, one with SLC26A4 variants, and one with an MITF variant. We demonstrated that PGD can be successfully applied to HHI of different inheritance modes, namely autosomal dominant or recessive, and phenotypes, namely syndromic or non-syndromic HHI. However, certain ethical concerns warrant scrutiny before PGD can be widely applied to at-risk couples with a history of HHI.

scholarly journals A simple method to estimate the in-house limit of detection for genetic mutations with low allele frequencies in whole-exome sequencing analysis by next-generation sequencing

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Takumi Miura ◽  
Satoshi Yasuda ◽  
Yoji Sato
Keyword(s):  
Next Generation Sequencing ◽  
Allele Frequency ◽  
Somatic Mutations ◽  
Limit Of Detection ◽  
Allele Frequencies ◽  
Genetic Mutations ◽  
Sequencing Data ◽  
Simple Method ◽  
Whole Exome ◽  
Generation Sequencing

Abstract Background Next-generation sequencing (NGS) has profoundly changed the approach to genetic/genomic research. Particularly, the clinical utility of NGS in detecting mutations associated with disease risk has contributed to the development of effective therapeutic strategies. Recently, comprehensive analysis of somatic genetic mutations by NGS has also been used as a new approach for controlling the quality of cell substrates for manufacturing biopharmaceuticals. However, the quality evaluation of cell substrates by NGS largely depends on the limit of detection (LOD) for rare somatic mutations. The purpose of this study was to develop a simple method for evaluating the ability of whole-exome sequencing (WES) by NGS to detect mutations with low allele frequency. To estimate the LOD of WES for low-frequency somatic mutations, we repeatedly and independently performed WES of a reference genomic DNA using the same NGS platform and assay design. LOD was defined as the allele frequency with a relative standard deviation (RSD) value of 30% and was estimated by a moving average curve of the relation between RSD and allele frequency. Results Allele frequencies of 20 mutations in the reference material that had been pre-validated by droplet digital PCR (ddPCR) were obtained from 5, 15, 30, or 40 G base pair (Gbp) sequencing data per run. There was a significant association between the allele frequencies measured by WES and those pre-validated by ddPCR, whose p-value decreased as the sequencing data size increased. By this method, the LOD of allele frequency in WES with the sequencing data of 15 Gbp or more was estimated to be between 5 and 10%. Conclusions For properly interpreting the WES data of somatic genetic mutations, it is necessary to have a cutoff threshold of low allele frequencies. The in-house LOD estimated by the simple method shown in this study provides a rationale for setting the cutoff.

scholarly journals Hereditary Hearing Impairment with Cutaneous Abnormalities

Genes ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 43
Author(s):  
Tung-Lin Lee ◽  
Pei-Hsuan Lin ◽  
Pei-Lung Chen ◽  
Jin-Bon Hong ◽  
Chen-Chi Wu
Keyword(s):  
Connective Tissue ◽  
Hearing Impairment ◽  
Early Identification ◽  
Database Search ◽  
Connective Tissue Disorders ◽  
Cutaneous Manifestations ◽  
Genetic Causes ◽  
Profound Influence ◽  
Pubmed Database ◽  
Hereditary Hearing Impairment

Syndromic hereditary hearing impairment (HHI) is a clinically and etiologically diverse condition that has a profound influence on affected individuals and their families. As cutaneous findings are more apparent than hearing-related symptoms to clinicians and, more importantly, to caregivers of affected infants and young individuals, establishing a correlation map of skin manifestations and their underlying genetic causes is key to early identification and diagnosis of syndromic HHI. In this article, we performed a comprehensive PubMed database search on syndromic HHI with cutaneous abnormalities, and reviewed a total of 260 relevant publications. Our in-depth analyses revealed that the cutaneous manifestations associated with HHI could be classified into three categories: pigment, hyperkeratosis/nail, and connective tissue disorders, with each category involving distinct molecular pathogenesis mechanisms. This outline could help clinicians and researchers build a clear atlas regarding the phenotypic features and pathogenetic mechanisms of syndromic HHI with cutaneous abnormalities, and facilitate clinical and molecular diagnoses of these conditions.

scholarly journals The Evolving Field of Genetic Epidemiology: From Familial Aggregation to Genomic Sequencing

2019 ◽  
Vol 188 (12) ◽  
pp. 2069-2077
Author(s):  
Priya Duggal ◽  
Christine Ladd-Acosta ◽  
Debashree Ray ◽  
Terri H Beaty
Keyword(s):  
Genetic Epidemiology ◽  
Disease Risk ◽  
Familial Aggregation ◽  
Rna Expression ◽  
Entire Genome ◽  
The Past ◽  
Future Challenges ◽  
The Individual ◽  
Study Designs ◽  
Health Applications

Abstract The field of genetic epidemiology is relatively young and brings together genetics, epidemiology, and biostatistics to identify and implement the best study designs and statistical analyses for identifying genes controlling risk for complex and heterogeneous diseases (i.e., those where genes and environmental risk factors both contribute to etiology). The field has moved quickly over the past 40 years partly because the technology of genotyping and sequencing has forced it to adapt while adhering to the fundamental principles of genetics. In the last two decades, the available tools for genetic epidemiology have expanded from a genetic focus (considering 1 gene at a time) to a genomic focus (considering the entire genome), and now they must further expand to integrate information from other “-omics” (e.g., epigenomics, transcriptomics as measured by RNA expression) at both the individual and the population levels. Additionally, we can now also evaluate gene and environment interactions across populations to better understand exposure and the heterogeneity in disease risk. The future challenges facing genetic epidemiology are considerable both in scale and techniques, but the importance of the field will not diminish because by design it ties scientific goals with public health applications.

Sign in / Sign up

Export Citation Format

Share Document