Generation of a human iPS cell line (CGMH.SLC26A4919-2) from a Pendred syndrome patient carrying SLC26A4 c.919-2A&gt;G splice-site mutation

Chan, Yu-Chang; Hu, C. K.; Lu, Ying Chang; Saeki, Tsubasa; Saegusa, Chika; Fujioka, Masato; Weng, Shih Ming; Hsu, Chia-Jui; Chang, Kuo Hsuan; Wu, Chen‐Chi

doi:10.1016/j.scr.2019.101524

Cited by 9 publications

(5 citation statements)

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“…Among the 98 deafness-related genes detected in this study, SLC26A4 (62.7%, 32/51), MYO15A (63.6%, 14/22), OTOF (40.0%, 4/10) and PTPRQ (75.0%, 3/4) contained intronic variants. In previous studies, it has been confirmed that the intron of SLC26A4 is prone to mutations, especially at the c.919-2A > G site, which is one of the mutation hotspots in the Asian population [ 24 , 25 ]. Our research also confirmed this.…”

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%

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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“…Progressive HL has also been reported in mice harbouring the mutated human TMEM 43 sequence [ 112 ]. On the other hand, other types of HL, such as PDS, lack appropriate animal models [ 10 , 113 ], and patient-derived hiPSC lines will therefore provide highly valuable information [ 36 , 114 , 115 ]. Although no progressive deafness is observed in any of the rodent models for PDS [ 9 ], a degenerative phenotype has been described by Hosoya and colleagues on outer sulcus cell (OSC)-like cells derived from hiPSCs generated from PDS patients with mutated Pendrin/ SLC 26A4 (Solute Carrier Family 26 Member 4) alleles [ 36 ].…”

Section: Hipscs To Generate Genetic Models Of Hlmentioning

confidence: 99%

Induced Pluripotent Stem Cells, a Stepping Stone to In Vitro Human Models of Hearing Loss

Alonso

Petković

2022

Cells

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Hearing loss is the most prevalent sensorineural impairment in humans. Yet despite very active research, no effective therapy other than the cochlear implant has reached the clinic. Main reasons for this failure are the multifactorial nature of the disorder, its heterogeneity, and a late onset that hinders the identification of etiological factors. Another problem is the lack of human samples such that practically all the work has been conducted on animals. Although highly valuable data have been obtained from such models, there is the risk that inter-species differences exist that may compromise the relevance of the gathered data. Human-based models are therefore direly needed. The irruption of human induced pluripotent stem cell technologies in the field of hearing research offers the possibility to generate an array of otic cell models of human origin; these may enable the identification of guiding signalling cues during inner ear development and of the mechanisms that lead from genetic alterations to pathology. These models will also be extremely valuable when conducting ototoxicity analyses and when exploring new avenues towards regeneration in the inner ear. This review summarises some of the work that has already been conducted with these cells and contemplates future possibilities.

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“…In the inner ear, pendrin is thought to modulate Cl − /HCO 3 − exchange and is therefore responsible for the conditioning of endolymphatic fluid, presumably due to HCO3 − secretion (Wangemann et al, 2007). The mutation c.919‐2A>G is the most frequent hot‐spot mutation of the SLC26A4 gene in the Chinese deaf population, and it is the second most common mutation in other Asian countries (Cheng et al, 2019). Guangxi is an area inhabited by ethnic minorities, mainly the Zhuang people.…”

Section: Inrtoductionmentioning

confidence: 99%

A novel SLC26A4 splicing mutation identified in two deaf Chinese twin sisters with enlarged vestibular aqueducts

Zhou

Huang

Feng

et al. 2020

Molec Gen & Gen Med

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Generation of a human iPS cell line (CGMH.SLC26A4919-2) from a Pendred syndrome patient carrying SLC26A4 c.919-2A>G splice-site mutation

Cited by 9 publications

References 4 publications

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

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

Induced Pluripotent Stem Cells, a Stepping Stone to In Vitro Human Models of Hearing Loss

A novel SLC26A4 splicing mutation identified in two deaf Chinese twin sisters with enlarged vestibular aqueducts

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