Abstract

Aim: To characterise the phenotype and identify the underlying genetic defect in a family with deafness segregating with a North Carolina-like macular dystrophy (NCMD).

Methods: Details of the family were obtained from the Moorfields Eye Hospital genetic clinic database and comprised eight affected, four unaffected members, and two spouses. Pedigree data were collated and leucocyte DNA extracted from venous blood. Positional candidate gene and genetic linkage strategies utilising polymerase chain reaction (PCR) based microsatellite marker genotyping were performed to identify the disease locus.

Results: The non-progressive ocular phenotype shared similarities with North Carolina macular dystrophy. Electro-oculography and full field electroretinography were normal. Progressive sensorineural deafness was also present in all affected individuals over the age of 20 years. Hearing was normal in all unaffected relatives. Haplotype analysis indicated that this family is unrelated to previously reported families with NCMD. Genotyping excluded linkage to the MCDR1 locus and suggested a potential novel disease locus on chromosome 14q (Z=2.92 at 𝛉=0 for marker D14S261).

Conclusion: The combination of anomalies segregating in this family represents a novel phenotype. This molecular analysis indicates the disease is genetically distinct from NCMD.