Genomic analysis of inherited hearing loss in the Palestinian population

Rayyan, Amal Abu; Kamal, Lara; Casadei, Silvia; Brownstein, Zippora; Zahdeh, Fouad; Shahin, Hashem; Canavati, Christina; Dweik, Dima; Jaraysa, Tamara; Rabie, Grace; Carlson, Ryan J.; Gülsüner, Süleyman; Lee, Ming K.; Avraham, Karen B.; Walsh, Tom; King, Mary Claire; Kanaan, Moien

doi:10.1073/pnas.2009628117

Cited by 37 publications

(29 citation statements)

References 41 publications

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“…To date, more than 190 pathologic variants have been reported for the Usher phenotype and 200 pathologic variants for the non-syndromic hearing loss phenotype (DFNB12) (Stenson et al 2003). CDH23-related hearing loss has been reported in many countries with diverse ethnic backgrounds, including Cuba (Bolz et al 2001), Germany (Bolz et al 2001), Japan (Wagatsuma et al 2007;Miyagawa et al 2012;Mizutari et al 2015), Korea (Kim et al 2015(Kim et al , 2016, China (Lu et al 2014), India (Bork et al 2001;Ganapathy et al 2014;Vanniya et al 2018), Pakistan (Bork et al 2001;Park et al 2020), Saudi Arabia (Ramzan et al 2020), Iran (Zardadi et al 2020), Qatar (Alkowari et al 2017), Turkey (Atik et al 2015), Israel (Ashkenazi, Mizurahi, Sephardi) (Brownstein et al 2011), Palestine (Abu Rayyan et al 2020) and the Netherlands (Seco et al 2017).…”

Section: Introductionmentioning

confidence: 99%

Variants in CDH23 cause a broad spectrum of hearing loss: from non-syndromic to syndromic hearing loss as well as from congenital to age-related hearing loss

et al. 2022

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Variants in the CDH23 gene are known to be responsible for both syndromic hearing loss (Usher syndrome type ID: USH1D) and non-syndromic hearing loss (DFNB12). Our series of studies demonstrated that CDH23 variants cause a broad range of phenotypes of non-syndromic hearing loss (DFNB12); from congenital profound hearing loss to late-onset high-frequency-involved progressive hearing loss. In this study, based on the genetic and clinical data from more than 10,000 patients, the mutational spectrum, clinical characteristics and genotype/phenotype correlations were evaluated. The present results reconfirmed that the variants in CDH23 are an important cause of non-syndromic sensorineural hearing loss. In addition, we showed that the mutational spectrum in the Japanese population, which is probably representative of the East Asian population in general, as well as frequent CDH23 variants that might be due to some founder effects. The present study demonstrated CDH23 variants cause a broad range of phenotypes, from non-syndromic to syndromic hearing loss as well as from congenital to age-related hearing loss. Genotype (variant combinations) and phenotype (association with retinal pigmentosa, onset age) are shown to be well correlated and are thought to be related to the residual function defined by the CDH23 variants.

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Section: Introductionmentioning

confidence: 99%

Variants in CDH23 cause a broad spectrum of hearing loss: from non-syndromic to syndromic hearing loss as well as from congenital to age-related hearing loss

et al. 2022

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“…In the context of molecular genetic testing, gene panel sequencing using MPS is a powerful strategy to identify causal variants, including single-nucleotide variants, insertions, deletions or CNVs in patients referred for NSHL [ 20 , 21 , 22 ]. Custom computational tools have been successfully used to detect CNVs in hearing gene panels [ 15 , 21 , 23 ], but detection of true single-exon or partial exon deletions is still challenging.…”

Section: Discussionmentioning

confidence: 99%

Identification of the First Single GSDME Exon 8 Structural Variants Associated with Autosomal Dominant Hearing Loss

et al. 2022

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GSDME, also known as DFNA5, is a gene implicated in autosomal dominant nonsyndromic hearing loss (ADNSHL), affecting, at first, the high frequencies with a subsequent progression over all frequencies. To date, all the GSDME pathogenic variants associated with deafness lead to skipping of exon 8. In two families with apparent ADNSHL, massively parallel sequencing (MPS) integrating a coverage-based method for detection of copy number variations (CNVs) was applied, and it identified the first two causal GSDME structural variants affecting exon 8. The deleterious impact of the c.991-60_1095del variant, which includes the acceptor splice site sequence of exon 8, was confirmed by the study of the proband’s transcripts. The second mutational event is a complex rearrangement that deletes almost all of the exon 8 sequence. This study increases the mutational spectrum of the GSDME gene and highlights the crucial importance of MPS data for the detection of GSDME exon 8 deletions, even though the identification of a causal single-exon CNV by MPS analysis is still challenging.

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“…TRIOBP various is rare in HL patients. There are 45 disease-related variants have been reported in the TRIOBP at present ( Hashem et al, 2006 ; Saima et al, 2006 ; Maiko et al, 2013 ; Shearer et al, 2014 ; Christina et al, 2016 ; Denise et al, 2016 ; Manou et al, 2016 ; Agnieszka et al, 2017 ; Celia et al, 2017 ; Daniel et al, 2017 ; Haiqiong et al, 2018 ; Elodie et al, 2019 ; Songfeng et al, 2019 ; Yan et al, 2019 ; Amal et al, 2020 ; Birgit et al, 2020 ; Yongyi et al, 2020 ), with HL being the only phenotypic manifestation. As presented in Table 1 , although the variants cover the region from exon 4 to exon 23, most of the previously reported variations in TRIOBP are located in exon 7.…”

Section: Discussionmentioning

confidence: 99%

Case Report: Novel Compound Heterozygous Variants in TRIOBP Associated With Congenital Deafness in a Chinese Family

et al. 2021

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Autosomal recessive non-syndromic deafness-28 (DFNB28) is characterized by prelingual, profound sensorineural hearing loss (HL). The disease is related to variants of the TRIOBP gene. TRIO and F-actin binding protein (TRIOBP) plays crucial roles in modulating the assembly of the actin cytoskeleton and are responsible for the proper structure and function of stereocilia in the inner ear. This study aimed to identify pathogenic variants in a patient with HL. Genomic DNA obtained from a 33-year-old woman with HL was evaluated using a disease-targeted gene panel. Using next generation sequencing and bioinformatics analysis, we identified two novel TRIOBP c.1170delC (p.S391Pfs*488) and c.3764C > G (p.S1255*) variants. Both parents of the patient were heterozygous carriers of the gene. The two variants have not been reported in general population databases or published literature. The findings of this study will broaden the spectrum of pathogenic variants in the TRIOBP gene.

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Genomic analysis of inherited hearing loss in the Palestinian population

Cited by 37 publications

References 41 publications

Variants in CDH23 cause a broad spectrum of hearing loss: from non-syndromic to syndromic hearing loss as well as from congenital to age-related hearing loss

Variants in CDH23 cause a broad spectrum of hearing loss: from non-syndromic to syndromic hearing loss as well as from congenital to age-related hearing loss

Identification of the First Single GSDME Exon 8 Structural Variants Associated with Autosomal Dominant Hearing Loss

Case Report: Novel Compound Heterozygous Variants in TRIOBP Associated With Congenital Deafness in a Chinese Family

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