Reproductive guidance through prenatal diagnosis and genetic counseling for recessive hereditary hearing loss in high-risk families

Deng, Yuyuan; Sang, Shushan; Wen, Jie; Ling, Jie; Chen, Hong-Sheng; Cai, Xinzhang; Mei, Lingyun; Xiaoya, Chen; Li, Meng; Li, Wu; Li, Taoxi; He, Chufeng

doi:10.1016/j.ijporl.2018.08.026

Cited by 3 publications

(4 citation statements)

References 37 publications

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“…Thus, this strategy can be applied to numerous ARNSHL patients at hearing clinics to yield a genetic diagnosis. Acquiring a genetic diagnosis of HL may offer a wealth of benefits such as making individualized health instruction, providing genetic counseling, and evaluating the recurrence rate of HL, offering detailed information for pre-natal diagnosis and preimplantation genetic diagnosis (PGD), as we have validated in a previous study (Deng et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

“…For congenital or early-onset HL, genetic factor is considered to be the dominant etiology (Nance, 2003; Wang et al, 2018), especially for those with a family history. Among hereditary cases, approximately 70% are NSHL, for which hearing impairment is the exclusive phenotype (Niu et al, 2017; Deng et al, 2018). It is reported that almost 80% of NSHL cases involve autosomal-recessive inheritance with high genetic heterogeneity (Angeli et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

“…It is reported that almost 80% of NSHL cases involve autosomal-recessive inheritance with high genetic heterogeneity (Angeli et al, 2012). The major symptom of autosomal-recessive NSHL (ARNSHL) is bilaterally symmetric, severe-to-profound, and prelingual sensorineural HL, which is known to be caused mainly by monogenic mutations (Wu et al, 2016; Deng et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

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Proband Whole-Exome Sequencing Identified Genes Responsible for Autosomal Recessive Non-Syndromic Hearing Loss in 33 Chinese Nuclear Families

et al. 2019

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Autosomal recessive non-syndromic hearing loss (ARNSHL) is a highly heterogeneous disease involving more than 70 pathogenic genes. However, most ARNSHL families have small-sized pedigrees with limited genetic information, rendering challenges for the molecular diagnosis of these patients. Therefore, we attempted to establish a strategy for identifying deleterious variants associated with ARNSHL by applying proband whole-exome sequencing (proband-WES). Aside from desiring to improve molecular diagnostic rates, we also aimed to search for novel deafness genes shared by patients with similar phenotype, making up for the deficiency of small ARNSHL families. In this study, 48.5% (16/33) families were detected the pathogenic variants in eight known deafness genes, including 10 novel variants identified in TMPRSS3 (MIM 605551), MYO15A (MIM 602666), TMC1 (MIM 606706), ADGRV1 (MIM 602851), and PTPRQ (MIM 603317). Apart from six novel variants with a truncating effect (nonsense, deletion, insertion, and splice-site), four novel missense variants were not found in 200 unrelated control population by using Sanger sequencing. It is important to note that none of novel genes were shared across different pedigrees, indicating that a larger sample size might be needed. Proband-WES is a cost-effective and precise way of identifying causative variants in nuclear families with ARNSHL. This economical strategy may be appropriated as a clinical application to provide molecular diagnostics, genetic counseling, and individualized health maintenance measures for patients with ARNSHL at hearing clinics.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Proband Whole-Exome Sequencing Identified Genes Responsible for Autosomal Recessive Non-Syndromic Hearing Loss in 33 Chinese Nuclear Families

et al. 2019

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“…For both congenital or prelingual deafness, genetic factors are considered to be the dominant etiology [2], especially for those with a family history. Approximately, 70% of the hereditary deafness cases can be classi ed as non-syndromic hearing loss (NSHL), for which hearing loss is the only phenotype [3]. In recent years, many gene variations have been con rmed to be related to deafness.…”

Section: Introductionmentioning

confidence: 99%

Molecular etiology of hereditary deafness using next generation sequencing in northwest China

Wang¹,

Li²,

Ding³

et al. 2020

Preprint

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Objective: To analyze the molecular etiology of 92 hereditary deafness families and explore the genetic mechanism of newly identified genes in deafness heritability. Methods: We analyzed the medical history, audiology, imaging, and physical examination data of 92 probands and their family members. Probands were selected from the hereditary deafness database; they did not have any of the common genetic mutation sites. Genomic DNA was extracted from blood samples and next generation sequencing was performed on an Illumina platform, followed by co-segregation analysis of family members. The control group included the clinical data and blood samples from 207 normal hearing people. Results: Among the 92 samples, 30 homozygous variants were identified in 29 autosomal recessive hereditary deafness families, including 6 reported mutations and 26 novel mutations. Among them, MYO15A was the most frequently detected (6/92), followed by mutations in CDH23, OTOF, FGF3 (3/92 each), MYO7A, SLC26A4, MYO6 (2/92 each), BSND, CLDN14, DFNB59, ILDR1, LHFPL5, LRTOMT, TMPRSS3, TPRN, USH1C, and LOXHD1 (1/92 each). Conclusion: In patients with autosomal recessive deafness, the MYO15A, CDH23, OTOF, and FGF3 genes could be used as candidate genes for conventional genetic studies in northwest China.

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Clinical Genetic Testing for Hearing Loss: Implications for Genetic Counseling and Gene-Based Therapies

Lee,

Uhler,

Yoon

et al. 2024

Biomedicines

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Genetic factors contribute significantly to congenital hearing loss, with non-syndromic cases being more prevalent and genetically heterogeneous. Currently, 150 genes have been associated with non-syndromic hearing loss, and their identification has improved our understanding of auditory physiology and potential therapeutic targets. Hearing loss gene panels offer comprehensive genetic testing for hereditary hearing loss, and advancements in sequencing technology have made genetic testing more accessible and affordable. Currently, genetic panel tests available at a relatively lower cost are offered to patients who face financial barriers. In this study, clinical and audiometric data were collected from six pediatric patients who underwent genetic panel testing. Known pathogenic variants in MYO15A, GJB2, and USH2A were most likely to be causal of hearing loss. Novel pathogenic variants in the MYO7A and TECTA genes were also identified. Variable hearing phenotypes and inheritance patterns were observed amongst individuals with different pathogenic variants. The identification of these variants contributes to the continually expanding knowledge base on genetic hearing loss and lays the groundwork for personalized treatment options in the future.

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Reproductive guidance through prenatal diagnosis and genetic counseling for recessive hereditary hearing loss in high-risk families

Cited by 3 publications

References 37 publications

Proband Whole-Exome Sequencing Identified Genes Responsible for Autosomal Recessive Non-Syndromic Hearing Loss in 33 Chinese Nuclear Families

Proband Whole-Exome Sequencing Identified Genes Responsible for Autosomal Recessive Non-Syndromic Hearing Loss in 33 Chinese Nuclear Families

Molecular etiology of hereditary deafness using next generation sequencing in northwest China

Clinical Genetic Testing for Hearing Loss: Implications for Genetic Counseling and Gene-Based Therapies

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