Deafness, Autosomal Recessive 1A

Last update 08 May 2025

Basic Info

Synonyms

DEAFNESS, AUTOSOMAL RECESSIVE 1A, DEAFNESS, AUTOSOMAL RECESSIVE 1A (disorder), DFNB1A

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Introduction

An autosomal recessive disorder caused by mutations in the GJB2 gene, encoding gap junction beta-2 protein. The condition is characterized by profound sensorineural hearing loss and may be associated with vestibular dysfunction.

Clinical Trials associated with Deafness, Autosomal Recessive 1A

NCT05402813

/ RecruitingNot Applicable

Longitudinal Study of the Natural History of Two Autosomal Recessive Non Syndromic Deafness (DFNB1A and DFNB9) in Children Up to 16 Years of Age

The purpose of this study is to follow the natural history of non-syndromic hearing loss caused by mutations in two genes (GJB2 or OTOF) in children up to 16 years of age.

Start Date18 Nov 2022

Sponsor / Collaborator

Sensorion SA

100 Clinical Results associated with Deafness, Autosomal Recessive 1A

100 Translational Medicine associated with Deafness, Autosomal Recessive 1A

0 Patents (Medical) associated with Deafness, Autosomal Recessive 1A

Literatures (Medical) associated with Deafness, Autosomal Recessive 1A

20 Jun 2024·Nan fang yi ke da xue xue bao = Journal of Southern Medical University

[Carrier screening for 223 monogenic diseases in Chinese population: a multi-center study in 33 104 individuals].

Article

Author: Fu, X ; Mao, X ; Zhao, Y ; Bian, J ; Jiang, Y ; Li, S ; Zhu, Q ; Luo, C ; Zhang, C ; Yuan, J ; Hou, W ; Jin, H ; Xie, X ; Wen, J ; Zhang, M ; Qian, Y ; Lu, Y ; Yin, A ; Qi, Q ; Xiao, R

OBJECTIVETo investigate the epidemiological characteristics and mutation spectrum of monogenic diseases in Chinese population through a large-scale, multicenter carrier screening.METHODSThis study was conducted among a total of 33 104 participants (16 610 females) from 12 clinical centers across China.Carrier status for 223 genes was analyzed using high-throughput sequencing and different PCR methods.RESULTSThe overall combined carrier frequency was 55.58% for 197 autosomal genes and 1.84% for 26 X-linked genes in these participants.Among the 16 669 families, 874 at-risk couples (5.24%) were identified.Specifically, 584 couples (3.50%) were at risk for autosomal genes, 306(1.84%) for X-linked genes, and 16 for both autosomal and X-linked genes.The most frequently detected autosomal at-risk genes included GJB2(autosomal recessive deafness type 1A, 393 couples), HBA1/HBA2(α-thalassemia, 36 couples), PAH (phenylketonuria, 14 couples), and SMN1(spinal muscular atrophy, 14 couples).The most frequently detected X-linked at-risk genes were G6PD (G6PD deficiency, 236 couples), DMD (Duchenne muscular dystrophy, 23 couples), and FMR1(fragile X syndrome, 17 couples).After excluding GJB2 c.109G>A, the detection rate of at-risk couples was 3.91%(651/16 669), which was lowered to 1.72%(287/16 669) after further excluding G6PD.The theoretical incidence rate of severe monogenic birth defects was approximately 4.35‰(72.5/16 669).Screening for a battery of the top 22 most frequent genes in the at-risk couples could detect over 95% of at-risk couples, while screening for the top 54 genes further increased the detection rate to over 99%.CONCLUSIONThis study reveals the carrier frequencies of 223 monogenic genetic disorders in the Chinese population and provides evidence for carrier screening strategy development and panel design tailored to the Chinese population.In carrier testing, genetic counseling for specific genes or gene variants can be challenging, and the couples need to be informed of these difficulties before testing and provided with options for not screening these genes or gene variants.

13 May 2023·Cellular and molecular life sciences : CMLS

The pathogenesis of common Gjb2 mutations associated with human hereditary deafness in mice

Article

Author: Lv, Jun ; Li, Jinsong ; Li, Qing ; Wang, Xiaohan ; Zhao, Jingjing ; Wang, Liqin ; Tang, Wei ; Li, Huawei ; Yin, Xidi ; Liao, Rongyu ; Yan, Meng ; Zhou, Jinan ; Wang, Yingyi ; Cheng, Yanbo ; Shu, Yilai ; Huang, Bowei ; Cui, Chong ; Wang, Daqi

Mutations in GJB2 (Gap junction protein beta 2) are the most common genetic cause of non-syndromic hereditary deafness in humans, especially the 35delG and 235delC mutations. Owing to the homozygous lethality of Gjb2 mutations in mice, there are currently no perfect mouse models carrying Gjb2 mutations derived from patients for mimicking human hereditary deafness and for unveiling the pathogenesis of the disease. Here, we successfully constructed heterozygous Gjb2^+/35delG and Gjb2^+/235delC mutant mice through advanced androgenic haploid embryonic stem cell (AG-haESC)-mediated semi-cloning technology, and these mice showed normal hearing at postnatal day (P) 28. A homozygous mutant mouse model, Gjb2^{35delG/35delG}, was then generated using enhanced tetraploid embryo complementation, demonstrating that GJB2 plays an indispensable role in mouse placenta development. These mice exhibited profound hearing loss similar to human patients at P14, i.e., soon after the onset of hearing. Mechanistic analyses showed that Gjb2 35delG disrupts the function and formation of intercellular gap junction channels of the cochlea rather than affecting the survival and function of hair cells. Collectively, our study provides ideal mouse models for understanding the pathogenic mechanism of DFNB1A-related hereditary deafness and opens up a new avenue for investigating the treatment of this disease.

01 Jan 2023·Clinica Chimica Acta

Amplicon sequencing-based carrier screening for 170 monogenic disorders among children with abnormal LC-MS/MS results

Article

Author: Liang, Hui ; Wu, Feng ; Xu, Zhongyao ; Chen, Xu ; Xiong, Likuan ; Lei, Xianghua ; Guo, Yongchao ; Chen, Ruoqing

BACKGROUNDNext-generation sequencing (NGS) has been suggested as a second-tier diagnostic test for newborn screening, which could help identify the carrier status of hundreds monogenic disorders with wider spectrum and earlier stage.METHODSAmong the 1087 children (age from 27 min to 14 years old) underwent liquid chromatography-tandem mass spectrometry (LC-MS/MS), 290 individuals who had at least one abnormal value of LC-MS/MS measurements were sent for amplicon sequencing-based carrier screening (targeting 141 genes for 170 monogenic disorders). Multiplex polymerase chain reaction was used for amplicon capture and library preparation, the NextSeq 500 NGS platform (Illumina PE150) was used for sequencing. The identified clinical significant variants were further validated by Sanger sequencing.RESULTSOnly 89 children carry none of clinical significant variants, other 201 individuals carry 1-4 variants in 63 genes (132 types; 317 in total: 171 pathogenic, 37 likely pathogenic, 29 variants of unknown significance, and 80 disease-associated functional polymorphisms). Besides the three missing samples with 4 variants, 91.1 % of identified variants (285 variants in 54 genes) were completely validated by Sanger sequencing. The most common genetic variants were in UGT1A1, GJB2, PAH, G6PD, and SLC25A13 (top 5 genes), which corresponding to Gilbert/Crigler-Najjar symdrome (n = 89), autosomal recessive hearing loss type 1A (n = 58), phenylketonuria (n = 12), glucose-6-phosphate dehydrogenease deficiency (n = 11) and Citrin deficiency (n = 9). More than 42 children present higher phenylalanine in LC-MS/MS, but only 12 of them were identified to carry clinical significant variants in PAH gene.CONCLUSIONThe amplicon sequencing-based carrier screening in our study could further clarify the abnormal LC-MS/MS results, which could also discover more monogenic disorders uncovered by LC-MS/MS screening.

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Deafness, Autosomal Recessive 1A

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