Rising of LOXHD1 as a signature causative gene of down-sloping hearing loss in people in their teens and 20s

2021 ◽  
pp. jmedgenet-2020-107594
Author(s):  
Bong Jik Kim ◽  
Hyoung Won Jeon ◽  
Woosung Jeon ◽  
Jin Hee Han ◽  
Jayoung Oh ◽  
...  
Keyword(s):  
Young Adults ◽  
Hearing Loss ◽  
Three Dimensional ◽  
Phenotype Correlation ◽  
Causative Gene ◽  
Genotype Phenotype Correlation ◽  
National University ◽  
Common Founder ◽  
Seoul National University ◽  
Efficient Learning

BackgroundDown-sloping sensorineural hearing loss (SNHL) in people in their teens and 20s hampers efficient learning and communication and in-depth social interactions. Nonetheless, its aetiology remains largely unclear, with the exception of some potential causative genes, none of which stands out especially in people in their teens and 20s. Here, we examined the role and genotype–phenotype correlation of lipoxygenase homology domain 1 (LOXHD1) in down-sloping SNHL through a cohort study.MethodsBased on the Seoul National University Bundang Hospital (SNUBH) genetic deafness cohort, in which the patients show varying degrees of deafness and different onset ages (n=1055), we have established the ‘SNUBH Teenager–Young Adult Down-sloping SNHL’ cohort (10–35 years old) (n=47), all of whom underwent exome sequencing. Three-dimensional molecular modelling, minigene splicing assay and short tandem repeat marker genotyping were performed, and medical records were reviewed.ResultsLOXHD1 accounted for 33.3% of all genetically diagnosed cases of down-sloping SNHL (n=18) and 12.8% of cases in the whole down-sloping SNHL cohort (n=47) of young adults. We identified a potential common founder allele, as well as an interesting genotype–phenotype correlation. We also showed that transcript 6 is necessary and probably sufficient for normal hearing.ConclusionsLOXHD1 exceeds other genes in its contribution to down-sloping SNHL in young adults, rising as a signature causative gene, and shows a potential but interesting genotype–phenotype correlation.

Novel TECTA Mutations Identified in Stable Sensorineural Hearing Loss and Their Clinical Implications

2014 ◽  
Vol 20 (1) ◽  
pp. 17-25 ◽  
Author(s):  
Ah Reum Kim ◽  
Mun Young Chang ◽  
Ja-Won Koo ◽  
Seung Ha Oh ◽  
Byung Yoon Choi
Keyword(s):  
Hearing Loss ◽  
Sensorineural Hearing Loss ◽  
High Frequency ◽  
Autosomal Dominant ◽  
Sensorineural Hearing ◽  
Clinical Feature ◽  
Phenotype Correlation ◽  
Causative Gene ◽  
Bioinformatics Analyses ◽  
Genotype Phenotype Correlation

TECTA is a causative gene of autosomal dominant (DFNA8/A12) and autosomal recessive (DFNB 21) nonsyndromic sensorineural hearing loss (NSHL). Mutations in TECTA account for 4% of all autosomal dominant NSHL cases in some populations and are thus thought to be one of the major causes of autosomal dominant NSHL. A genotype-phenotype correlation for autosomal dominant mutations in the TECTA gene has been proposed. Two families (SB146 and SB149), which segregated moderate NSHL in an autosomal dominant fashion, were included in this study. We performed targeted resequencing of 134 known deafness genes (TRS-134) and bioinformatics analyses to find causative mutations for NSHL in these 2 families. Through TRS-134, we detected 2 novel mutations, i.e. c.3995G>T (p.C1332F) and c.5618C>T (p.T1873I), in the TECTA gene. These mutations cosegregated with NSHL in the studied families and were not detected in normal controls. The mutations c.3995G>T and c.5618C>T reside in the von Willebrand factor type D3-D4 (vWFD3-D4) interdomain of the zonadhesin (ZA) domain and the zona pellucida (ZP) domain, respectively. p.C1332F is the first mutation detected in the vWFD3-D4 interdomain of the ZA domain. The mutations p.C1332F and p.T1873I were associated with stable high-frequency and mid-frequency hearing loss, respectively. Notably, the cysteine residue mutated to phenylalanine in SB146 was not related to progression of sensorineural hearing loss, which argues against the previous hypothesis. Here we confirm a known genotype-phenotype correlation for the ZP domain and propose a hypothetical genotype-phenotype correlation which relates mutations in vWFD3-D4 to stable high-frequency NSHL in Koreans. This clinical feature makes subjects with the missense mutation in the vWFD3-D4 interdomain of TECTA potentially good candidates for middle ear implantation. i 2014 S. Karger AG, Basel

scholarly journals GJB2 Mutation Spectrum and Genotype-Phenotype Correlation in 1067 Han Chinese Subjects with Non-Syndromic Hearing Loss

PLoS ONE ◽  
2015 ◽  
Vol 10 (6) ◽  
pp. e0128691 ◽  
Author(s):  
Jing Zheng ◽  
Zhengbiao Ying ◽  
Zhaoyang Cai ◽  
Dongmei Sun ◽  
Zheyun He ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Han Chinese ◽  
Mutation Spectrum ◽  
Phenotype Correlation ◽  
Gjb2 Mutation ◽  
Genotype Phenotype Correlation ◽  
Syndromic Hearing Loss ◽  
Chinese Subjects

scholarly journals A novel KCNQ4 one-base deletion in a large pedigree with hearing loss: implication for the genotype–phenotype correlation

2006 ◽  
Vol 51 (5) ◽  
pp. 455-460 ◽  
Author(s):  
Fumiaki Kamada ◽  
Shigeo Kure ◽  
Takayuki Kudo ◽  
Yoichi Suzuki ◽  
Takeshi Oshima ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Phenotype Correlation ◽  
Large Pedigree ◽  
Genotype Phenotype Correlation

scholarly journals Detailed clinical features and genotype–phenotype correlation in an OTOF-related hearing loss cohort in Japan

2021 ◽  
Author(s):  
Yoh-ichiro Iwasa ◽  
Shin-ya Nishio ◽  
Hidekane Yoishimura ◽  
Akiko Sugaya ◽  
Yuko Kataoka ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Cochlear Implantation ◽  
Clinical Characteristics ◽  
Clinical Information ◽  
Auditory Neuropathy ◽  
Hearing Level ◽  
Phenotype Correlation ◽  
Profound Hearing Loss ◽  
Genotype Phenotype Correlation ◽  
Auditory Performance

AbstractMutations in the OTOF gene are a common cause of hereditary hearing loss and the main cause of auditory neuropathy spectrum disorder (ANSD). Although it is reported that most of the patients with OTOF mutations have stable, congenital or prelingual onset severe-to-profound hearing loss, some patients show atypical clinical phenotypes, and the genotype–phenotype correlation in patients with OTOF mutations is not yet fully understood. In this study, we aimed to reveal detailed clinical characteristics of OTOF-related hearing loss patients and the genotype–phenotype correlation. Detailed clinical information was available for 64 patients in our database who were diagnosed with OTOF-related hearing loss. As reported previously, most of the patients (90.6%) showed a “typical” phenotype; prelingual and severe-to-profound hearing loss. Forty-seven patients (73.4%) underwent cochlear implantation surgery and showed successful outcomes; approximately 85–90% of the patients showed a hearing level of 20–39 dB with cochlear implant and a Categories of Auditory Performance (CAP) scale level 6 or better. Although truncating mutations and p.Arg1939Gln were clearly related to severe phenotype, almost half of the patients with one or more non-truncating mutations showed mild-to-moderate hearing loss. Notably, patients with p.His513Arg, p.Ile1573Thr and p.Glu1910Lys showed “true” auditory neuropathy-like clinical characteristics. In this study, we have clarified genotype–phenotype correlation and efficacy of cochlear implantation for OTOF-related hearing loss patients in the biggest cohort studied to date. We believe that the clinical characteristics and genotype–phenotype correlation found in this study will support preoperative counseling and appropriate intervention for OTOF-related hearing loss patients.

Novel genotype–phenotype correlation of functionally characterized LMX1A variants linked to sensorineural hearing loss

2020 ◽  
Vol 41 (11) ◽  
pp. 1877-1883 ◽  
Author(s):  
Sang‐Yeon Lee ◽  
Jin Hee Han ◽  
Marge Carandang ◽  
Min Young Kim ◽  
Bonggi Kim ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Sensorineural Hearing Loss ◽  
Sensorineural Hearing ◽  
Phenotype Correlation ◽  
Genotype Phenotype Correlation ◽  
Novel Genotype
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