<i>DFNB86</i>, a novel autosomal recessive non‐syndromic deafness locus on chromosome 16p13.3

Ali, Rizwana; Au, Rehman; Sn, Khan; Husnain, Tayyab; Riazuddin, Sheikh; Tb, Friedman; Ahmed, Zaheer

doi:10.1111/j.1399-0004.2011.01729.x

Cited by 9 publications

(4 citation statements)

References 9 publications

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“…S1) with the maximum LOD score of 3.80 obtained for marker rs7187438. This interval overlaps with that reported for the recessive nonsyndromic deafness locus DFNB86 [Ali et al., ].…”

supporting

confidence: 82%

A Dominant Mutation in the Stereocilia-Expressing GeneTBC1D24is a Probable Cause for Nonsyndromic Hearing Impairment

Zhang

Chai

et al. 2014

Human Mutation

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Mutations in TBC1D24 have been linked to a variety of epileptic syndromes and recently to syndromic hearing impairment DOORS syndrome and nonsyndromic hearing impairment DFNB86. All TBC1D24 mutations reported so far were inherited in the recessive mode. In a dominant family segregated with late-onset, progressive, nonsyndromic hearing impairment, linkage analysis revealed a 2.07 Mb candidate region on chromosome 16p13.3 that contains TBC1D24. Whole-exome sequencing identified a heterozygous p.Ser178Leu variant of TBC1D24 as the only candidate mutation segregating with the hearing loss within the family. In perinatal mouse cochlea, we detected a restricted expression of Tbc1d24 in the stereocilia of the hair cells as well as in the spiral ganglion neurons. Our study suggested that the p.Ser178Leu mutation of TBC1D24 is a probable cause for dominant, nonsyndromic hearing impairment. Identification of TBC1D24 as the stereocilia-expressing gene may shed new light on its specific function in the inner ear.

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“…S1) with the maximum LOD score of 3.80 obtained for marker rs7187438. This interval overlaps with that reported for the recessive nonsyndromic deafness locus DFNB86 [Ali et al., ].…”

supporting

confidence: 82%

A Dominant Mutation in the Stereocilia-Expressing GeneTBC1D24is a Probable Cause for Nonsyndromic Hearing Impairment

Zhang

Chai

et al. 2014

Human Mutation

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“…As illustrated in Figure , seven of 26 mutations of TBC1D24 are associated with non‐syndromic deafness (i.e. no additional clinical anomalies) (Ali et al , ; Azaiez et al , ; Rehman et al , ; Zhang et al , ; Bakhchane et al , ). There are also ten mutant alleles of TBC1D24 reported in patients with epileptic syndromes (Corbett et al , ; Falace et al , ; Afawi et al , ; Guven and Tolun, ; Milh et al , ; Doummar et al , ; Muona et al , ; Poulat et al , ; Strazisar et al , ).…”

Section: Tbc1d24 Mutations Associated With Non‐syndromic Deafness Epmentioning

confidence: 99%

Unresolved questions regarding human hereditary deafness

Rehman

Griffith

2016

Oral Diseases

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Human hearing loss is a common neurosensory disorder about which many basic research and clinically relevant questions are unresolved. This review on hereditary deafness focuses on three examples considered at first glance to be uncomplicated, however, upon inspection, are enigmatic and ripe for future research efforts. The three examples of clinical and genetic complexities are drawn from studies of (1) Pendred syndrome/DFNB4 (PDS, OMIM 274600), (2) Perrault syndrome (deafness and infertility) due to mutations of CLPP (PRTLS3, OMIM 614129), and (3) the unexplained extensive clinical variability associated with TBC1D24 mutations. At present, it is unknown how different mutations of TBC1D24 cause nonsyndromic deafness (DFNB86, OMIM 614617), epilepsy (OMIM 605021), epilepsy with deafness, or DOORS syndrome (OMIM 220500) that is characterized by deafness, onychodystrophy (alteration of toenail or fingernail morphology), osteodystrophy (defective development of bone), intellectual disability and seizures. A comprehensive understanding of the multifaceted roles of each gene associated with human deafness is expected to provide future opportunities for restoration as well as preservation of normal hearing.

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“…15,16 Genome-wide homozygosity mapping of DFNB in a large consanguineous Pakistani family (PKDF799) identified the locus DFNB86 on chromosome 16p with a maximum LOD score of 8.5. 17 In this study, three additional consanguineous pedigrees (DEM4221, DEM4587, and DEM4476) from Pakistan were ascertained (inbreeding coefficients, Table S1, available online), and their recessive deafness was linked to DFNB86 with maximum LOD scores of 6.90, 3.26, and 5.97, respectively. The overlapping region of homozygosity of these four pedigrees spans 2.05 Mb and contains 121 annotated genes (Figure 1).…”

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confidence: 99%

“…Pure-tone audiometric evaluations of 4 of the 11 affected individuals from family PKDF799 revealed profound deafness (hearing threshold R 90 dB) at all test frequencies, whereas obligate carriers had normal hearing thresholds. 17 Genomic DNA samples from three affected individuals (IV-23 from family PKDF799, IV-11 from family DEM4221, and IV-6 from family DEM4476) were processed for whole-exome sequencing (WES; Figure 2). For family PKDF799, a TargetSeq Exome Enrichment Kit (Applied Biosystems) was used for capturing the whole exome (45.1 Mb), which was sequenced on an Applied Biosystems SOLiD5500 platform.…”

mentioning

confidence: 99%

Mutations in TBC1D24, a Gene Associated With Epilepsy, Also Cause Nonsyndromic Deafness DFNB86

Rehman

Santos‐Cortez

Morell

et al. 2014

The American Journal of Human Genetics

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Inherited deafness is clinically and genetically heterogeneous. We recently mapped DFNB86, a locus associated with nonsyndromic deafness, to chromosome 16p. In this study, whole-exome sequencing was performed with genomic DNA from affected individuals from three large consanguineous families in which markers linked to DFNB86 segregate with profound deafness. Analyses of these data revealed homozygous mutation c.208G>T (p.Asp70Tyr) or c.878G>C (p.Arg293Pro) in TBC1D24 as the underlying cause of deafness in the three families. Sanger sequence analysis of TBC1D24 in an additional large family in which deafness segregates with DFNB86 identified the c.208G>T (p.Asp70Tyr) substitution. These mutations affect TBC1D24 amino acid residues that are conserved in orthologs ranging from fruit fly to human. Neither variant was observed in databases of single-nucleotide variants or in 634 chromosomes from ethnically matched control subjects. TBC1D24 in the mouse inner ear was immunolocalized predominantly to spiral ganglion neurons, indicating that DFNB86 deafness might be an auditory neuropathy spectrum disorder. Previously, six recessive mutations in TBC1D24 were reported to cause seizures (hearing loss was not reported) ranging in severity from epilepsy with otherwise normal development to epileptic encephalopathy resulting in childhood death. Two of our four families in which deafness segregates with mutant alleles of TBC1D24 were available for neurological examination. Cosegregation of epilepsy and deafness was not observed in these two families. Although the causal relationship between genotype and phenotype is not presently understood, our findings, combined with published data, indicate that recessive alleles of TBC1D24 can cause either epilepsy or nonsyndromic deafness.

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DFNB86, a novel autosomal recessive non‐syndromic deafness locus on chromosome 16p13.3

Cited by 9 publications

References 9 publications

A Dominant Mutation in the Stereocilia-Expressing GeneTBC1D24is a Probable Cause for Nonsyndromic Hearing Impairment

A Dominant Mutation in the Stereocilia-Expressing GeneTBC1D24is a Probable Cause for Nonsyndromic Hearing Impairment

Unresolved questions regarding human hereditary deafness

Mutations in TBC1D24, a Gene Associated With Epilepsy, Also Cause Nonsyndromic Deafness DFNB86

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