Cone-Rod Dystrophy 12

A number sign (#) is used with this entry because of evidence that cone-rod dystrophy-12 (CORD12) is caused by homozygous or heterozygous mutation in the PROM1 gene (604365) on chromosome 4p15.

For a general phenotypic description and a discussion of genetic heterogeneity of cone-rod dystrophy, see 120970.

Clinical Features

Eidinger et al. (2015) reported 3 sibs, born to consanguineous Jewish parents of Kurdish Iraqi descent, with autosomal recessive cone-rod dystrophy. The sibs had progressive visual loss, central scotomas, photosensitivity, deficient color saturation, and slowly decreasing night vision. Cone and rod ERG responses were reduced, with cones more severely affected.

Mapping

Yang et al. (2008) performed linkage analysis in a 4-generation family segregating autosomal dominant cone-rod dystrophy characterized by both cone and rod photoreceptor degeneration and obtained a lod score of 4.4 on chromosome 4p.

Molecular Genetics

In a 4-generation family segregating autosomal dominant cone-rod dystrophy mapping to chromosome 4p, Yang et al. (2008) identified heterozygosity for a missense mutation in the PROM1 gene (604365.0003). The authors identified the same mutation in a family with Stargardt disease (STGD4; 603786) and a family with retinal macular dystrophy (MCDR2; 608051); the mutation was not found in 400 matched controls.

In 2 sibs with CORD12 from a consanguineous Arab Christian family (MOL0256), Beryozkin et al. (2014) identified homozygosity for a nonsense mutation (L386X; 604365.0004) in the PROM1 gene.

In 3 sibs with CORD12 from a consanguineous Jewish family (TB126) of Kurdish Iraqi descent, Eidinger et al. (2015) identified homozygosity for a 10-bp deletion (604365.0005) in intron 1 of the PROM1 gene. The deletion segregated with the disease in the family and was not detected in public databases or in 101 ethnically-matched control individuals.