Homozygous mutation in MERTK causes severe autosomal recessive retinitis pigmentosa.

PURPOSE: Gene identification in retinitis pigmentosa is a prerequisite to future therapies. Accordingly, autosomal recessive retinitis pigmentosa families were genotyped to search for causative mutations.

METHODS: Members of a consanguineous Moroccan family had standard ophthalmologic examination, optical coherence tomography-3 scan, autofluorescence testing, and electroretinogram. Their DNA was genotyped with the 250K SNP microchip (Affymetrix) and homozygosity mapping was done. MERTK exons were polymerase chain reaction amplified and sequenced.

RESULTS: Two sisters and one brother out of 6 siblings had rod cone dystrophy type of retinitis pigmentosa. Salient features were night blindness starting in early infancy, dot-like whitish deposits in fovea and macula with corresponding autofluorescent dots in youngest patients, decreased visual acuity, and cone responses higher than rod responses at electroretinogram. The patients were homozygous in regions from chromosomes 2 and 8, but only that of chromosome 2 was inherited from a common ancestor. Sequencing of the MERTK gene belonging to the chromosome 2 region showed that the 3 affected patients carried a novel homozygous mutation in exon 17, c.2323C>T, leading to p.Arg775X, while their unaffected brothers and sister, parents, and paternal grandfather were heterozygous.

CONCLUSIONS: MERTK mutations lead to severe retinitis pigmentosa with discrete dot-like autofluorescent deposits at early stages, which are a hallmark of this MERTK-specific dystrophy.