Deafness, Autosomal Recessive 2

Alternative Names

  • DFNB2
  • Neurosensory Nonsyndromic Recessive Deafness 2
  • NSRD2

Associated Genes

Myosin VIIA
Back to search Result
WHO-ICD-10 version:2010

Diseases of the ear and mastoid process

Other disorders of ear

OMIM Number

600060

Mode of Inheritance

Autosomal recessive

Gene Map Locus

11q13.5

Description

Sensorineural hearing loss (SNHL) is the most prevalent genetic sensory defect in humans. It is estimated that globally one out of every one thousand children born have profound hearing loss. Of those cases with genetic etiology, approximately 70% are non-syndromic. In addition, 80% of the non-syndromic SNHL cases are recessively inherited (ARNSHL), also known as DFNB. To date, few dozens of genes and gene loci have been implicated in DFNB.

DFNB2 is a form of neurosensory deafness with variable vestibular dysfunction. The age of onset of DFNB2 is usually at birth, but may occur later in life.

Molecular Genetics

DFNB2 is caused by homozygous or compound heterozygous mutation in the myosin VIIA gene (MYO7A) on chromosome 11q13.5. The MYO7A gene encodes a protein classified as an unconventional myosin, expressed in retinal photoreceptors and the retinal pigmented epithelium, as well as in cochlear and vestibular neuroepithelia. In the inner ear, this protein might maintain the rigidity of stereocilia during the dynamic movements of the bundle. It also participates in anchoring and holding membrane-bound elements to the actin core of the stereocilium. It is, therefore, required for the normal gating of transducer channels.

Mutations in the MYO7A gene are also found to be responsible for syndromic form of deafness, called Usher syndrome type Ib, which is clinically characterized by congenital profound deafness, progressive retinal degeneration, called retinitis pigmentosa (RP), and vestibular areflexia. Researchers suspect that the deafness cases with MYO7A mutations may actually represent early forms of Usher syndrome. It is not known whether all children with MYO7A mutations and hearing loss will develop retinitis pigmentosa later in life.

Epidemiology in the Arab World

View Map
Subject IDCountrySexFamily HistoryParental ConsanguinityHPO TermsVariantZygosityMode of InheritanceReferenceRemarks
600060.1.1PalestineMaleYesYes Prelingual sensorineural hearing impairm...NM_000260.4:c.6487G>AHomozygousAutosomal, RecessiveShahin et al. 2010
600060.1.2PalestineFemaleYesYes Prelingual sensorineural hearing impairm...NM_000260.4:c.6487G>AHomozygousAutosomal, RecessiveShahin et al. 2010 Sister of 600060.1.1
600060.1.3PalestineMaleYesYes Prelingual sensorineural hearing impairm...NM_000260.4:c.6487G>AHomozygousAutosomal, RecessiveShahin et al. 2010 Brother of 600060.1....
600060.2IraqMaleYes Infantile sensorineural hearing impairme...NM_000260.4:c.1952_1953insAGHomozygousAutosomal, RecessiveBen-Salem et al. 2014
600060.3.1United Arab EmiratesMaleYes Infantile sensorineural hearing impairme...NM_000260.4:c.5660C>THeterozygous, HomozygousAutosomal, RecessiveBen-Salem et al. 2014
600060.3.2United Arab EmiratesMaleYes Infantile sensorineural hearing impairme...NM_000260.4:c.5660C>THeterozygous, HomozygousAutosomal, RecessiveBen-Salem et al. 2014 Sibling of 600060.3....
600060.3.3United Arab EmiratesMaleYes Infantile sensorineural hearing impairme...NM_000260.4:c.5660C>THomozygousAutosomal, RecessiveBen-Salem et al. 2014 Sibling of 600060.3....
600060.3.4United Arab EmiratesMaleYes Congenital sensorineural hearing impairm...NM_000260.4:c.5660C>THeterozygous, HomozygousAutosomal, RecessiveBen-Salem et al. 2014 First cousin once re...
600060.3.5United Arab EmiratesFemaleYes Congenital sensorineural hearing impairm...NM_000260.4:c.5660C>THeterozygous, HomozygousAutosomal, RecessiveBen-Salem et al. 2014 Sibling of 600060.3....
600060.3.6United Arab EmiratesFemaleYes Congenital sensorineural hearing impairm...NM_000260.4:c.5660C>THeterozygous, HomozygousAutosomal, RecessiveBen-Salem et al. 2014 Sibling of 600060.3....
600060.G.1United Arab EmiratesUnknown Congenital sensorineural hearing impairm...NM_000260.4:c.223G>THomozygousAutosomal, RecessiveElsayed O and Al-Shamsi A. 2022 Three patients
600060.G.2United Arab EmiratesUnknown Congenital sensorineural hearing impairm...NC_000011.10:g.76917135_76917255HomozygousAutosomal, RecessiveElsayed O and Al-Shamsi A. 2022 Two patients with de...

Other Reports

Algeria

Ammar-Khodja et al. (2009) applied a systematic approach, involving haplotyping and genotyping, to depict the molecular etiology of non-syndromic deafness in 50 families and 9 sporadic cases from Algeria. One family with non-syndromic deafness carried a novel unclassified variant of unknown pathogenic effect in the MYO7A gene implicated in DFNB2.

Tunisia

Guilford et al. (1994) reported a consanguineous family from southern Tunisia in which 22 individuals had autosomal recessive non-syndromic sensorineural deafness. All had profound deafness, and 4 also had vertigo. The age of onset of deafness was variable and reported to range from birth to age 16 years. Linkage analysis demonstrated a possible linkage to chromosome 11q13 (maximum lod score of 10.63 at marker D11S527). Homozygosity mapping refined the location of the locus to a 6-cM interval that also contained the olfactory marker protein gene (OMP). The murine homolog of OMP is tightly linked to the autosomal recessive deafness shaker-1 gene in mice, suggesting that the deafness in this Tunisian family is the human homolog of the mouse shaker-1 mutation.

Later, Weil et al. (1997) identified a homozygous mutation in the MYO7A gene in affected members of the Tunisian family reported by Guilford et al. (1994). Much later, Zina et al. (2001) reevaluated the family reported by Guilford et al. (1994) and Weil et al. (1997). Since the original reports, five patients had developed mild retinal degeneration in addition to the progressive deafness. Fundus examination of one patient showed spicule pigmentary changes consistent with retinal dystrophy. Another previously unaffected family member, homozygous for the mutation, had retinitis pigmentosa. Seven patients had abnormal vestibular function as assessed by caloric tests. Zina et al. (2001) concluded that some patients in this Tunisian family had features consistent with Usher syndrome type IB. The findings suggested that other factors must modulate the expression of the phenotype.

© CAGS 2024. All rights reserved.