The interpretation of the targeted next‐generation sequencing (NGS) results can be challenging for variants identified in the sporadic deaf patients. In this study, we performed targeted NGS of 143 deafness‐associated genes in 44 sporadic deaf patients and use parental genotyping to test whether the candidate pathogenic variants complied with recessive or de novo pattern. Of 29 recessive candidate variants with minor allele frequencies (MAFs) less than 0.005, 3 pairs of apparent compound heterozygous variants were inherited from the same parental allele, ruling out their pathogenic roles. In addition, non‐segregation of an OTOA p.Gln293Arg variant led to the discovery of a genomic microdeletion of OTOA on the opposite allele by copy number variation analysis. Overall, 13 pairs of recessive candidate variants were deemed causative in 13 patients. Of the 28 dominant candidate variants with MAFs less than 0.0005, none occurred de novo, suggesting that they were not disease causing. Our results revealed that targeted NGS in sporadic deaf patients may generate a significant false‐positive rate. Parental genotyping is a simple but effective step toward minimizing the false‐positive results. Our study also showed that de novo variants in dominant deafness genes may not be a common cause for sporadic deafness.
Clinical Genetics – Wiley
Published: Jan 1, 2018
Keywords: ; ; ; ;
It’s your single place to instantly
discover and read the research
that matters to you.
Enjoy affordable access to
over 18 million articles from more than
15,000 peer-reviewed journals.
All for just $49/month
Query the DeepDyve database, plus search all of PubMed and Google Scholar seamlessly
Save any article or search result from DeepDyve, PubMed, and Google Scholar... all in one place.
Get unlimited, online access to over 18 million full-text articles from more than 15,000 scientific journals.
Read from thousands of the leading scholarly journals from SpringerNature, Elsevier, Wiley-Blackwell, Oxford University Press and more.
All the latest content is available, no embargo periods.
“Hi guys, I cannot tell you how much I love this resource. Incredible. I really believe you've hit the nail on the head with this site in regards to solving the research-purchase issue.”Daniel C.
“Whoa! It’s like Spotify but for academic articles.”@Phil_Robichaud
“I must say, @deepdyve is a fabulous solution to the independent researcher's problem of #access to #information.”@deepthiw
“My last article couldn't be possible without the platform @deepdyve that makes journal papers cheaper.”@JoseServera