The reference OMIM entry for this protein is 600652

Deafness, autosomal dominant 4a; dfna4a
Deafness, autosomal dominant 4; dfna4

A number sign (#) is used with this entry because autosomal dominant nonsyndromic deafness-4A (DFNA4A) is caused by heterozygous mutation in the MYH14 gene (608568) on chromosome 19q13.33. DFNA4B (614614), another autosomal dominant nonsyndromic deafness phenotype mapping to chromosome 19q13, is caused by mutation in the CEACAM16 gene (614591) at 19q13.32.

CLINICAL FEATURES

Mirghomizadeh et al. (2002) reported a 5-generation German family segregating nonsyndromic autosomal dominant hearing impairment. Affected individuals showed a progressive sensorineural hearing impairment, beginning in the first to the second decade and leading to severe to profound deafness in the fourth decade of their lives.

MAPPING

Using polymorphic microsatellite markers in a linkage study of a family segregating autosomal dominant nonsyndromic deafness, Chen et al. (1995) mapped the disorder locus, which they designated DFNA4, to chromosome 19q13. In a 5-generation German family segregating nonsyndromic autosomal dominant hearing impairment, Mirghomizadeh et al. (2002) performed a genomewide scan with microsatellite polymorphisms and found linkage to markers in the 19q13.3-q13.4 region. Key recombinations were identified in the family, reducing the disease-specific haplotype to a 14-cM interval between markers D19S412 and D19S571. This region showed partial overlap with the previously reported DFNA4 critical region (Chen et al. (1995)). The BAX gene (600040) mapped to the disease-specific interval, but genomic sequencing of the coding regions and exon/intron boundaries excluded disease-related mutations.

MOLECULAR GENETICS

MYH14 was considered a strong candidate gene for hearing loss because it was located within the candidate region of the DFNA4 locus defined by Chen et al. (1995) and Mirghomizadeh et al. (2002). Donaudy et al. (2004) performed mutation screening of the MYH14 gene in 300 hearing-impaired patients from Italy, Spain, and Belgium, and in a German kindred linked to DFNA4. They identified 1 nonsense (608568.0001) and 2 missense (608568.0002-608568.0003) mutations in large pedigrees linked to DFNA4, as well as a de novo allele in a sporadic case (608568.0004). In affected members of a 4-generation German family with autosomal dominant nonsyndromic hearing loss, Yang et al. (2005) identified a missense mutation in the MYH14 gene (608568.0005). However, complete screening of the American family that originally defined the DFNA4 locus (Chen et al., 1995) revealed no mutations in the coding region of the MYH14 gene; genotyping of SNPs close to the MYH14 gene excluded it from the candidate region and defined a 19-Mb interval demarcated by D19S414 and SNP dbSNP rs648298. Yang et al. (2005) concluded that a second gene associated with autosomal dominant nonsyndromic deafness links to the DFNA4 locus (see DFNA4B, 614614). ... More on the omim web site

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Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 600652 was added.