A Founder Mutation in<i>MYO7A</i>Underlies a Significant Proportion of Usher Syndrome in Indigenous South Africans: Implications for the African Diaspora

Roberts, Lisa; George, Siddiqah; Greenberg, Jacquie; Ramesar, Raj

doi:10.1167/iovs.15-17028

Cited by 9 publications

(5 citation statements)

References 36 publications

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“…African individuals with hearing loss. This particular mutation has only been reported once before in a heterozygous Caucasian individual (Roberts et al, 2015).…”

Section: Usher Syndrome (Ush)mentioning

confidence: 72%

The genetic basis of deafness in populations of African descent

Rudman

Kabahuma

Bressler

et al. 2017

Journal of Genetics and Genomics

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Hearing loss is the most common sensorineural disorder worldwide and is associated with more than 1000 mutations in more than 90 genes. While mutations in genes such as GJB2 (gap-junction protein β 2) and GJB6 (gap-junction protein β 6) are highly prevalent in Caucasian, Asian, and Middle Eastern populations, they are rare in both native African populations and those of African descent. The objective of this paper is to review the current knowledge regarding the epidemiology and genetics of hearing loss in African populations with a focus on native sub-Saharan African populations. Environmental etiologies related to poor access to healthcare and perinatal care account for the majority of cases. Syndromic etiologies including Waardenburg, Pendred and Usher syndromes are uncommon causes of hearing loss in these populations. Of the non-syndromic causes, common mutations in GJB2 and GJB6 are rarely implicated in populations of African descent. Recent use of next-generation sequencing (NGS) has identified several candidate deafness genes in African populations from Nigeria and South Africa that are unique when compared to common causative mutations worldwide. Researchers also recently described a dominant mutation in MYO3a in an African American family with non-syndromic hearing loss. The use of NGS and specialized panels will aid in identifying rare and novel mutations in a more cost- and time-effective manner. The identification of common hearing loss mutations in indigenous African populations will pave the way for translation into genetic deafness research in populations of African descent worldwide.

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“…African individuals with hearing loss. This particular mutation has only been reported once before in a heterozygous Caucasian individual (Roberts et al, 2015).…”

Section: Usher Syndrome (Ush)mentioning

confidence: 72%

The genetic basis of deafness in populations of African descent

Rudman

Kabahuma

Bressler

et al. 2017

Journal of Genetics and Genomics

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“…The recent increase in the number of genetically screened cases has revealed that some patients harbor mutations in USH genes usually associated with a different subtype. For example, variants in MYO7A and CDH23 have been identified in patients diagnosed with USH2 [16][17][18][19][20], and USH1 and USH3 cases have been found to be caused by mutations in USH2A [16,17,20].…”

Section: The Genetic Heterogeneity Of Ushmentioning

confidence: 99%

Usher Syndrome: Genetics of a Human Ciliopathy

Fuster-García

García‐Bohórquez

Rodríguez-Muñoz

et al. 2021

IJMS

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Usher syndrome (USH) is an autosomal recessive syndromic ciliopathy characterized by sensorineural hearing loss, retinitis pigmentosa and, sometimes, vestibular dysfunction. There are three clinical types depending on the severity and age of onset of the symptoms; in addition, ten genes are reported to be causative of USH, and six more related to the disease. These genes encode proteins of a diverse nature, which interact and form a dynamic protein network called the “Usher interactome”. In the organ of Corti, the USH proteins are essential for the correct development and maintenance of the structure and cohesion of the stereocilia. In the retina, the USH protein network is principally located in the periciliary region of the photoreceptors, and plays an important role in the maintenance of the periciliary structure and the trafficking of molecules between the inner and the outer segments of photoreceptors. Even though some genes are clearly involved in the syndrome, others are controversial. Moreover, expression of some USH genes has been detected in other tissues, which could explain their involvement in additional mild comorbidities. In this paper, we review the genetics of Usher syndrome and the spectrum of mutations in USH genes. The aim is to identify possible mutation associations with the disease and provide an updated genotype–phenotype correlation.

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“…To determine whether the most prevalent mutations in our cohort shared haplotypes among affected families, we selected the following for haplotype analysis: three single intragenic nucleotide polymorphisms (SNPs), namely, rs6592706, rs948972 and rs11237122 (Roberts et al 2015), and three polymorphic markers spanning the USHB1 locus, namely, D11S787, D11S527 and D11S4186 (Adato et al 1997). The primers used are listed in Table S1.…”

Section: Haplotype Analysismentioning

confidence: 99%

Genotype–phenotype correlation in patients with Usher syndrome and pathogenic variants in MYO7A: implications for future clinical trials

Galbis-Martínez

Blanco‐Kelly

García‐García

et al. 2021

Acta Ophthalmologica

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Purpose: We aimed to establish correlations between the clinical features of a cohort of Usher syndrome (USH) patients with pathogenic variants in MYO7A, type of pathogenic variant, and location on the protein domain. Methods: Sixty-two USH patients from 46 families with biallelic variants in MYO7A were examined for visual and audiological features. Participants were evaluated based on self-reported ophthalmological history and ophthalmological investigations (computerized visual field testing, best-corrected visual acuity, and ophthalmoscopic and electrophysiological examination). Optical coherence tomography and fundus autofluorescence imaging were performed when possible. Auditory and vestibular functions were evaluated. Patients were classified according to the type of variant and the protein domain where the variants were located. Results: Most patients displayed a typical USH1 phenotype, that is, prelingual severe-profound sensorineural hearing loss, prepubertal retinitis pigmentosa (RP) and vestibular dysfunction. No statistically significant differences were observed for the variables analysed except for the onset of hearing loss due to the existence of two USH2 cases, defined as postlingual sensorineural hearing loss, postpubertal onset of RP, and absence of vestibular dysfunction, and one atypical case of USH. Conclusion: We were unable to find a correlation between genotype and phenotype for MYO7A. However, our findings could prove useful for the assessment of efficacy in clinical trials, since the type of MYO7A variant does not seem to change the onset, severity or course of visual disease.

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A Founder Mutation inMYO7AUnderlies a Significant Proportion of Usher Syndrome in Indigenous South Africans: Implications for the African Diaspora

Cited by 9 publications

References 36 publications

The genetic basis of deafness in populations of African descent

The genetic basis of deafness in populations of African descent

Usher Syndrome: Genetics of a Human Ciliopathy

Genotype–phenotype correlation in patients with Usher syndrome and pathogenic variants in MYO7A: implications for future clinical trials

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