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CARDIOMYOPATHY, DILATED, 1J; CMD1J

CARDIOMYOPATHY, DILATED, 1J; CMD1J

Alternative titles; symbolsCARDIOMYOPATHY, DILATED, WITH SENSORINEURAL HEARING LOSS, AUTOSOMAL DOMINANT▼ Clinical FeaturesSchonberger et al. (2000) described 2 k...

Alternative titles; symbols

  • CARDIOMYOPATHY, DILATED, WITH SENSORINEURAL HEARING LOSS, AUTOSOMAL DOMINANT

▼ Clinical Features
Schonberger et al. (2000) described 2 kindreds with autosomal dominant transmission and age-related penetrance of both sensorineural hearing loss and dilated cardiomyopathy (DCM) in the absence of other disorders. Moderate to severe hearing loss was evident by late adolescence, whereas ventricular dysfunction produced progressive congestive heart failure after the fourth decade.

▼ Mapping
Using DNA samples from their larger kindred (MCE) of 29 individuals to perform a genomewide linkage study, Schonberger et al. (2000) obtained a maximum lod of 4.88 at D6S2411 on chromosome 6q23-q24. The authors concluded that the disease locus must lie within a 2.8-cM interval between D6S975 and D6S292, a location that overlaps the nonsyndromic sensorineural hearing loss disease locus DFNA10 (601316).

In a kindred (MCE) with dilated cardiomyopathy and heart failure preceded by sensorineural hearing loss mapping to 6q23-q24, previously described by Schonberger et al. (2000), Schonberger et al. (2005) performed fine mapping that narrowed the critical interval to a 2.0-Mb region containing 8 known genes and several EST clusters.

▼ Molecular Genetics
In a large kindred (MCE) with dilated cardiomyopathy and hearing loss linked to chromosome 6q23-q24, Schonberger et al. (2000) analyzed the candidate gene epicardin (603306), which encodes a transcription factor expressed in the myocardium and cochlea, but no mutations were identified.

In a kindred (MCE) with dilated cardiomyopathy and heart failure preceded by sensorineural hearing loss originally described by Schonberger et al. (2000), Schonberger et al. (2005) analyzed the 3 candidate genes within a 2.0-Mb critical region of linkage that are expressed in both heart and cochlea, EYA4 (603550), SGK (602958), and TCF21 (603306), and identified a deletion in the EYA4 gene (603550.0003) that was present in all affected family members and absent from 300 control chromosomes. The authors noted that previously described mutations causing dilated cardiomyopathy affected structural proteins, whereas EYA4 is a transcriptional coactivator.

Tags: 6q23.2