Retinal Dystrophy With Or Without Extraocular Anomalies

A number sign (#) is used with this entry because of evidence that retinal dystrophy with or without extraocular anomalies (RDEOA) is caused by homozygous mutation in the RCBTB1 gene (607867) on chromosome 13q14.

Clinical Features

Coppieters et al. (2016) reported 6 families of varying ethnic backgrounds segregating autosomal recessive retinal dystrophy, in which affected individuals were homozygous for mutations in the RCBTB1 gene. In a consanguineous family of Turkish origin, 2 sisters and a maternal cousin exhibited severe retinal dystrophy with onset in the second decade of life that was deemed 'compatible with' retinitis pigmentosa (RP; see 268000). In addition, all 3 affected individuals had goiter, secondary amenorrhea, and mild intellectual disability, and the sisters' mother had goiter. Hormone analysis in the affected individuals was consistent with primary ovarian insufficiency. The other 5 families were ascertained from unsolved retinal dystrophy cases from 4 cohorts in the European Retinal Disease Consortium; in those families, the affected individuals exhibited progressive retinal dystrophy with central chorioretinal atrophy and peripheral pattern-like reticular dystrophy, with onset in the fourth or fifth decade of life. Electroretinography showed moderate alterations of all responses, indicating loss of both rods and cones, and responses worsened with age. Extraocular features reported in the latter patients included thyroid nodules in a Greek man, sensorineural hearing loss in a Greek father and son, and lung fibrosis in an Algerian woman. However, no extraocular features were reported in an affected Chinese man, or in 2 Italian sibs who carried the same mutation as the Greek man. Coppieters et al. (2016) noted that they could not exclude the possibility that mutations in other genes caused the nonocular phenotypes.

Molecular Genetics

In 2 sisters and a maternal cousin from a consanguineous Belgian family of Turkish origin with retinal dystrophy, goiter, and primary ovarian failure, Coppieters et al. (2016) performed whole-exome sequencing (WES) followed by Sanger sequencing and identified homozygosity for a missense mutation in the RCBTB1 gene (H325Y; 607867.0001) that segregated with disease in the family and was not found in 142 controls, including 68 of Turkish origin. Targeted next-generation sequencing in a Belgian cohort of 281 probands with autosomal recessive or sporadic retinal dystrophy did not reveal any mutations. Inspection of WES data from approximately 450 unsolved retinal dystrophy cases from the European Retinal Disease Consortium revealed homozygous missense mutations in the RCBTB1 gene in the probands from 5 additional families of Italian, Greek, Algerian, and Chinese origin (see, e.g., 607867.0002-607867.0004).