Molecular and phenotypic analysis of a family with autosomal recessive cone-rod dystrophy and Stargardt disease

PURPOSE: To identify the causative gene mutations in three siblings with severe progressive autosomal recessive cone-rod dystrophy (arCRD) and their fifth paternal cousin with Stargardt disease (STGD1) and to specify the phenotypes.

METHODS: We evaluated eight sibs of one family, three family members displayed arCRD, and one STGD1. All of them were screened for mutations using a new microarray for autosomal recessive retinitis pigmentosa.

RESULTS: We found a new pathologic ATP-binding cassette transporter (ABCA4) splice-site mutation, c.3523-2A>T and the previously reported c.5327C>T (p.P1776L) missense mutation in the arCRD patients. The three siblings shared these two ABCA4 mutations and showed similar phenotypes. An unusual aspect was nystagmus which presented in one of the arCRD patients. In the STGD1 patient we found the c.5327C>T (p.P1776L) missense mutation and a novel c.868C>T (p.R290W) missense mutation.

CONCLUSIONS: Two new ABCA4 mutations were identified in a family with arCRD and STGD1. A new finding was nystagmus associated with arCRD in one of the patients.