Background: We present 3 members of a family with macular dystrophy, originally diagnosed as Stargardt disease, with a significantly variable age at onset, caused by a heterozygous mutation in CRX.
Case presentation: A 43-year-old female with bull's eye maculopathy, whose sister was diagnosed with Stargardt disease previously at another centre, was found to have a single ABCA4 variant. Further examination of the family revealed that the asymptomatic father was also affected, indicating a dominant pattern of inheritance. In addition, the ABCA4 variant was not identified in the sister originally diagnosed with Stargardt disease. Next generation sequencing identified a heterozygous c.121C > T, p.R41W missense mutation in CRX in all 3 affected members.
Conclusions: We describe a common phenotype, but with variable age at onset, with autosomal dominant inheritance and reduced penetrance in a family found to have a pathogenic sequence variant in CRX. This illustrates the importance of panel based molecular genetic testing accompanied by family studies to establish a definitive diagnosis.
Keywords: ABCA4 sequence variant, mutation; CRX; Macular dystrophy; Next generation sequencing; Phenotype/genotype, reduced penetrance, family survey; Retina.