scholarly journals Identification of novel variants in Iranian consanguineous pedigrees with nonsyndromic hearing loss by next‐generation sequencing

2020 ◽  
Vol 34 (12) ◽  
Author(s):  
Fatemeh Bitarafan ◽  
Seyed Yousef Seyedena ◽  
Mahdi Mahmoudi ◽  
Masoud Garshasbi
Keyword(s):  
Hearing Loss ◽  
Next Generation Sequencing ◽  
Nonsyndromic Hearing Loss ◽  
Next Generation ◽  
Novel Variants ◽  
Generation Sequencing

scholarly journals Development and Validation of a Next-Generation Sequencing Panel for Syndromic and Nonsyndromic Hearing Loss

2020 ◽  
Vol 5 (3) ◽  
pp. 467-479 ◽  
Author(s):  
Malinda Butz ◽  
Amber McDonald ◽  
Patrick A Lundquist ◽  
Melanie Meyer ◽  
Sean Harrington ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Next Generation Sequencing ◽  
Copy Number Variants ◽  
Analytical Sensitivity ◽  
Nonsyndromic Hearing Loss ◽  
Next Generation ◽  
Single Nucleotide Variants ◽  
Small Indels ◽  
Syndromic Hearing Loss ◽  
Generation Sequencing

Abstract Background Deafness and hearing loss are common conditions that can be seen independently or as part of a syndrome and are often mediated by genetic causes. We sought to develop and validate a hereditary hearing loss panel (HHLP) to detect single nucleotide variants (SNVs), insertions and deletions (indels), and copy number variants (CNVs) in 166 genes related to nonsyndromic and syndromic hearing loss. Methods We developed a custom-capture next-generation sequencing (NGS) reagent to detect all coding regions, ±10 flanking bp, for the 166 genes related to nonsyndromic and syndromic hearing loss. Our validation consisted of testing 52 samples to establish accuracy, reproducibility, and analytical sensitivity. In addition to NGS, supplementary methods, including multiplex ligation-dependent probe amplification, long-range PCR, and Sanger sequencing, were used to ensure coverage of regions that had high complexity or homology. Results We observed 100% positive and negative percentage agreement for detection of SNVs (n = 362), small indels (1–22 bp, n = 25), and CNVs (gains, n = 8; losses, n = 17). Finally, we showed that this assay was able to detect variants with a variant allele frequency ≥20% for SNVs and indels and ≥30% to 35% for CNVs. Conclusions We validated an HHLP that detects SNVs, indels, and CNVs in 166 genes related to syndromic and nonsyndromic hearing loss. The results of this assay can be utilized to confirm a diagnosis of hearing loss and related syndromic disorders associated with known causal genes.

scholarly journals Next-generation sequencing reveals three novel variants in Polish patients with Usher syndrome

Klinika Oczna ◽  
2018 ◽  
Vol 2018 (4) ◽  
pp. 189-194
Author(s):  
Anna Wawrocka ◽  
Joanna Walczak-Sztulpa ◽  
Anna Skorczyk-Werner ◽  
Łukasz Kuszel ◽  
Magdalena Socha ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Usher Syndrome ◽  
Next Generation ◽  
Novel Variants ◽  
Generation Sequencing

scholarly journals A Novel Heterozygous Mutation of the COL4A3 Gene Causes a Peculiar Phenotype without Hematuria and Renal Function Impairment in a Chinese Family

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Liang Xia ◽  
Yangjia Cao ◽  
Yang Guo ◽  
Guangyi Ba ◽  
Qiong Luo ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Next Generation Sequencing ◽  
Collagen Iv ◽  
Chinese Family ◽  
Heterozygous Mutation ◽  
Next Generation ◽  
Structural Protein ◽  
Type Iv ◽  
Function Impairment ◽  
Generation Sequencing

Mutations in the COL4A3 gene are frequently reported to be associated with various types of hereditary nephropathy. COL4A3 encodes the α3 chain of type IV collagen, which is the main structural protein in the basement membrane. Mutations in this gene are always related to kidney performance, and deafness and ocular lesion have also been reported. In this study, using next-generation sequencing, we investigated the DNA of a family visiting a clinic for hearing loss. A new missense mutation was found in COL4A3 of 5 patients, c.3227C>T (p.P1076L). Based on these results, we predict that the mutation is pathogenic and leads to abnormal collagen IV. Here, we report for the first time on this autosomal dominant syndrome, characterized by hearing loss and eye abnormalities, but without renal damage, in all carriers. Since the oldest patient in the trial was less than 50 years old, however, we recommend that renal examination be reviewed regularly. Our results reveal expansion in the mutation spectrum of the COL4A3 gene and phenotypic spectrum of collagen IV disease. Our study suggests that next-generation sequencing is an economical and effective method and may help in the accurate diagnosis and treatment of these patients.

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