MERTK missense variants in three patients with retinitis pigmentosa.

BACKGROUND

is a transmembrane protein essential in regulating photoreceptor outer segment phagocytosis. Biallelic mutations in cause retinal degeneration. Here we present the retinal phenotype of three patients with missense variants in .

MATERIALS AND METHODS

All patients underwent a full clinical examination, fundus photography, short-wavelength fundus autofluorescence and optical coherence tomography imaging. Two patients also underwent Goldmann visual field testing and electroretinography was undertaken for the third patient. Molecular genetic testing was undertaken using next generation or whole-exome sequencing with all variants confirmed by Sanger sequencing.

RESULTS

The first patient was a 29-year-old female heterozygous for a missense variant (c.1133C>T, p.Thr378 Met) and a nonsense variant (c.1744_1751delinsT, p.Ile582Ter) in . The second patient was a 26-year-old male homozygous for a c.2163T>A, p.His721Gln variant in . The third patient was an 11-year-old female heterozygous for a deletion of exons 5-19 and a missense variant (c.1866 G>C, p.Lys622Asn) in . Reduced night vision was the initial symptom in all patients. Fundoscopy revealed typical signs of retinitis pigmentosa (RP) with early-onset macular atrophy. All three missense variants affect highly conserved residues within functional domains, have low population frequencies and are predicted to be pathogenic .

CONCLUSIONS

We report three missense variants in and present the associated phenotypic data, which are supportive of non-syndromic RP. is a promising candidate for viral-mediated gene replacement therapy. Moreover, one variant represents a single nucleotide transition, which is theoretically targetable with CRISPR-Cas9 base-editing.