A new locus for autosomal recessive non-syndromal sensorineural hearing impairment (DFNB27) on chromosome 2q23–q31

Pulleyn, Louise J.; Jackson, Andrew P.; Roberts, Emma; Carridice, A; Muxworthy, Claire; Houseman, M; Al‐Gazali, Lihadh; Lench, Nicholas; Markham, Alex F.; Mueller, Robin

doi:10.1038/sj.ejhg.5200567

Cited by 21 publications

(11 citation statements)

References 15 publications

(14 reference statements)

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“…1). At the time of initial investigation, the ARNSHL disease interval comprised 54 annotated genes (UCSC Genome Browser) and overlapped with the DFNB27 locus [Pulleyn et al, 2000]. After exclusion of mutations in 41 candidate genes from the ARNSHL candidate interval, we identified a homozygous 1-bp insertion in exon 2 of the DFNB59 gene (c.113_114insT) in the index patient (Patient II:5).…”

Section: Identi¢cation Of the Arnshl Locus And Mutation Analysis Of Tmentioning

confidence: 99%

Truncating mutation of theDFNB59gene causes cochlear hearing impairment and central vestibular dysfunction

et al. 2007

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We have identified a consanguineous family from Morocco segregating autosomal recessive congenital progressive hearing loss (ARNSHL) and retinal degeneration. Detailed clinical investigation of the six siblings revealed combined severe cone-rod dystrophy (CORD) and severe/profound hearing impairment in two of them, while there is isolated CORD in three and nonsyndromic profound hearing loss in one. We therefore assumed a partial overlap of two nonsyndromic autosomal recessive conditions instead of a monogenic syndrome and performed genomewide linkage analysis. The disease loci were mapped to chromosome 2q31.1-2q32.1 for ARNSHL and to 2q13-2q14.1 for CORD, respectively. The retinal phenotype was shown to be due to homozygosity for a novel splice site mutation, c.2189+1G>T, in the retinitis pigmentosa gene MERTK. The ARNSHL interval comprised the DFNB59 locus. The DFNB59 gene has been identified recently, and two missense mutations (p.R183W and p.T54I) have been shown to cause auditory neuropathy in both humans and transgenic mice. Mutation screening in the DFNB59 gene in our family revealed homozygosity for a 1-bp insertion in exon 2 (c.113_114insT), predicting a truncated protein of 47 amino acids, in all three hearing impaired subjects. This is the first description of biallelic putative loss-of-function of the DFNB59 gene. Detailed audiological investigation clearly indicated hair cell dysfunction and, in contrast to cases reported previously, excluded auditory neuropathy. We show that besides otoferlin (OTOF), DFNB59 is the second known gene in which mutations can result in these two distinct forms of hearing impairment. Moreover, all patients in our family with homozygosity for the DFNB59 mutation display central vestibular dysfunction.

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Section: Identi¢cation Of the Arnshl Locus And Mutation Analysis Of Tmentioning

confidence: 99%

Truncating mutation of theDFNB59gene causes cochlear hearing impairment and central vestibular dysfunction

et al. 2007

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“…Nonsyndromic deafness was present in 81% of cases and most of those (98%) had autosomal recessive type. However, the frequency of Connexin 26 mutations is not known, but two genes were mapped in two UAE consanguineous families to 15q21-q22 and 2q23-q31 [Campbell et al, 1997;Pulleyn et al, 2000]. In addition, a novel nonsense mutation (p.R237X) in the Otoferlin (OTOF) gene has been reported in another family [Houseman et al, 2001] (Table 10).…”

Section: Deafnessmentioning

confidence: 99%

Mutations of a country: a mutation review of single gene disorders in the United Arab Emirates (UAE)

Al‐Gazali

Ali

2010

Hum. Mutat.

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“…4 During the 1990s, microsatellite genome-wide linkage study in large families was used to map novel HI loci. [5][6][7] Since the first years of this century, higher throughput and cost-effective single-nucleotide polymorphism genome scans have been increasingly used in place of it. 8 Identification of corresponding HI-causing genes was based on functional candidate gene strategy and Sanger sequencing (pejv myo).…”

Section: Introductionmentioning

confidence: 99%

Genome-wide analysis reveals a novel autosomal-recessive hearing loss locus DFNB80 on chromosome 2p16.1-p21

et al. 2012

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Hearing impairment (HI) is the decreased ability to hear and discriminate among sounds. It is one of the most common birth defects. Epidemiological data show that more than one child in 1000 is born with HI, whereas more than 50% of prelingual HI cases are found to be hereditary. So far, 95 published autosomal-recessive nonsyndromic HI (ARNSHI) loci have been mapped, and 41 ARNSHI genes have been identified. In this study, we performed a genome-wide linkage study in a consanguineous Tunisian family, and report the mapping of a novel ARNSHI locus DFNB80 to chromosome 2p16.1-p21 between the two single-nucleotide polymorphisms rs10191091 and rs2193485 with a maximum multipoint logarithm of odds score of 4.1. The screening of seven candidate genes, failed to reveal any disease-causing mutations.

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A new locus for autosomal recessive non-syndromal sensorineural hearing impairment (DFNB27) on chromosome 2q23–q31

Cited by 21 publications

References 15 publications

Truncating mutation of theDFNB59gene causes cochlear hearing impairment and central vestibular dysfunction

Truncating mutation of theDFNB59gene causes cochlear hearing impairment and central vestibular dysfunction

Mutations of a country: a mutation review of single gene disorders in the United Arab Emirates (UAE)

Genome-wide analysis reveals a novel autosomal-recessive hearing loss locus DFNB80 on chromosome 2p16.1-p21

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