Whole-Genome Sequencing Improves the Diagnosis of DFNB1 Monoallelic Patients

Nabec, Anaïs Le; Collobert, Mégane; Maréchal, Cédric Le; Marianowski, R.; Férec, Claude; Moisan, Stéphanie

doi:10.3390/genes12081267

Cited by 5 publications

(1 citation statement)

References 43 publications

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“…The development of the Human Genome Project has promoted the combination of genetics and clinical medicine for diagnostics. The emergence of genetic screening and diagnosis for deafness is of great significance for the clarification of the cause of deafness and to prevent its occurrence [ 9 – 11 ]. Since the 1980s, with the development of technology, great progress has been made in the study of the genetic etiology of deafness.…”

Section: Discussionmentioning

confidence: 99%

Genetic screening of a Chinese cohort of children with hearing loss using a next-generation sequencing panel

Lin

et al. 2023

Hum Genomics

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Background At present, the hereditary hearing loss homepage, (https://hereditaryhearingloss.org/), includes 258 deafness genes and more than 500 genes that have been reported to cause deafness. With few exceptions, the region-specific distributions are unclear for many of the identified variants and genes. Methods Here, we used a custom capture panel to perform targeted sequencing of 518 genes in a cohort of 879 deaf Chinese probands who lived in Yunnan. Mutation sites of the parents were performed by high-throughput sequencing and validated by Sanger sequencing. Results The ratio of male to female patients was close to 1:1 (441:438) and the age of onset was mainly under six. Most patients (93.5%) were diagnosed with moderate to severe deafness. Four hundred and twenty-eight patients had variants in a deafness gene, with a detection rate of 48.7%. Pathogenic variants were detected in 98 genes and a number of these were recurrent within the cohort. However, many of the variants were rarely observed in the cohort. In accordance with the American College of Medical Genetics and Genomics, pathogenic, likely pathogenic and variants of uncertain significance accounted for 34.3%, 19.3% and 46.4% of all detected variants, respectively. The most common genes included GJB2, SLC26A4, MYO15A, MYO7A, TMC1, CDH23, USH2A and WFS1, which contained variants in more than ten cases. The two genes with the highest mutation frequency were GJB2 and SLC26A4, which accounted for 28.5% (122/428) of positive patients. We showed that more than 60.3% of coding variants were rare and novel. Of the variants that we detected, 80.0% were in coding regions, 17.9% were in introns and 2.1% were copy number variants. Conclusion The common mutation genes and loci detected in this study were different from those detected in other regions or ethnic groups, which suggested that genetic screening or testing programs for deafness should be formulated in accordance with the genetic characteristics of the region.

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Section: Discussionmentioning

confidence: 99%