Dataset Information

Comprehensive analysis of syndromic hearing loss patients in Japan.

ABSTRACT: More than 400 syndromes associated with hearing loss and other symptoms have been described, corresponding to 30% of cases of hereditary hearing loss. In this study we aimed to clarify the mutation spectrum of syndromic hearing loss patients in Japan by using next-generation sequencing analysis with a multiple syndromic targeted resequencing panel (36 target genes). We analyzed single nucleotide variants, small insertions, deletions and copy number variations in the target genes. We enrolled 140 patients with any of 14 syndromes (BOR syndrome, Waardenburg syndrome, osteogenesis imperfecta, spondyloepiphyseal dysplasia congenita, Stickler syndrome, CHARGE syndrome, Jervell and Lange-Nielsen syndrome, Pendred syndrome, Klippel-Feil syndrome, Alport syndrome, Norrie disease, Treacher-Collins syndrome, Perrault syndrome and auditory neuropathy with optic atrophy) and identified the causative variants in 56% of the patients. This analysis could identify the causative variants in syndromic hearing loss patients in a short time with a high diagnostic rate. In addition, it was useful for the analysis of the cases who only partially fulfilled the diagnostic criteria.

SUBMITTER: Ideura M

PROVIDER: S-EPMC6700179 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Comprehensive analysis of syndromic hearing loss patients in Japan.

Ideura Michie M Nishio Shin-Ya SY Moteki Hideaki H Takumi Yutaka Y Miyagawa Maiko M Sato Teruyuki T Kobayashi Yumiko Y Ohyama Kenji K Oda Kiyoshi K Matsui Takamichi T Ito Tsukasa T Suzumura Hiroshi H Nagai Kyoko K Izumi Shuji S Nishiyama Nobuhiro N Komori Manabu M Kumakawa Kozo K Takeda Hidehiko H Kishimoto Yoko Y Iwasaki Satoshi S Furutate Sakiko S Ishikawa Kotaro K Fujioka Masato M Nakanishi Hiroshi H Nakayama Jun J Horie Rie R Ohta Yumi Y Naito Yasushi Y Kakudo Mariko M Sakaguchi Hirofumi H Kataoka Yuko Y Sugahara Kazuma K Hato Naohito N Nakagawa Takashi T Tsuchihashi Nana N Kanda Yukihiko Y Kihara Chiharu C Tono Tetsuya T Miyanohara Ikuyo I Ganaha Akira A Usami Shin-Ichi SI

Scientific reports 20190819 1

More than 400 syndromes associated with hearing loss and other symptoms have been described, corresponding to 30% of cases of hereditary hearing loss. In this study we aimed to clarify the mutation spectrum of syndromic hearing loss patients in Japan by using next-generation sequencing analysis with a multiple syndromic targeted resequencing panel (36 target genes). We analyzed single nucleotide variants, small insertions, deletions and copy number variations in the target genes. We enrolled 140 ...[more]

PMID: 31427586

Similar Datasets

Project description:BackgroundSensorineural hearing loss (SNHL) is the most common sensory impairment. Comprehensive next-generation sequencing (NGS) has become the standard for the etiological diagnosis of early-onset SNHL. However, accurate selection of target genomic regions (gene panel/exome/genome), analytical performance and variant interpretation remain relevant difficulties for its clinical implementation.MethodsWe developed a novel NGS panel with 199 genes associated with non-syndromic and/or syndromic SNHL. We evaluated the analytical sensitivity and specificity of the panel on 1624 known single nucleotide variants (SNVs) and indels on a mixture of genomic DNA from 10 previously characterized lymphoblastoid cell lines, and analyzed 50 Spanish patients with presumed hereditary SNHL not caused by GJB2/GJB6, OTOF nor MT-RNR1 mutations.ResultsThe analytical sensitivity of the test to detect SNVs and indels on the DNA mixture from the cell lines was > 99.5%, with a specificity > 99.9%. The diagnostic yield on the SNHL patients was 42% (21/50): 47.6% (10/21) with autosomal recessive inheritance pattern (BSND, CDH23, MYO15A, STRC [n = 2], USH2A [n = 3], RDX, SLC26A4); 38.1% (8/21) autosomal dominant (ACTG1 [n = 3; 2 de novo], CHD7, GATA3 [de novo], MITF, P2RX2, SOX10), and 14.3% (3/21) X-linked (COL4A5 [de novo], POU3F4, PRPS1). 46.9% of causative variants (15/32) were not in the databases. 28.6% of genetically diagnosed cases (6/21) had previously undetected syndromes (Barakat, Usher type 2A [n = 3] and Waardenburg [n = 2]). 19% of genetic diagnoses (4/21) were attributable to large deletions/duplications (STRC deletion [n = 2]; partial CDH23 duplication; RDX exon 2 deletion).ConclusionsIn the era of precision medicine, obtaining an etiologic diagnosis of SNHL is imperative. Here, we contribute to show that, with the right methodology, NGS can be transferred to the clinical practice, boosting the yield of SNHL genetic diagnosis to 50-60% (including GJB2/GJB6 alterations), improving diagnostic/prognostic accuracy, refining genetic and reproductive counseling and revealing clinically relevant undiagnosed syndromes.

Dataset Information

Comprehensive analysis of syndromic hearing loss patients in Japan.

Publications

Comprehensive analysis of syndromic hearing loss patients in Japan.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets