Variable expressivity in patients with autosomal recessive retinitis pigmentosa associated with the gene .

PURPOSE

In a cohort of eight families (11 patients) with autosomal recessive retinitis pigmentosa (arRP), we clinically characterized disease associated with mutations in .

METHODS

Visual function was determined by measuring the patients' visual acuity, dark- and light-adapted perimetry, and by full-field electroretinography. Retinal structure was evaluated with spectral-domain optical coherence tomography, fundus imaging, and autofluorescence imaging.

RESULTS

Age of onset ranged from 4 to 49 years (mean [SD] 26 [17], median 27 years). The age at visit was 27-54 years, mean 37 (17). The range of visual acuity was logMAR -0.1 to 1.3 (Snellen 20/16 to 20/400) in the right eye and -0.1 to 0.9 (Snellen 20/16 to 20/160) in the left eye. Electrophysiological testing in five patients showed an absence of the rod response. Cone responses ranged from normal to severely reduced. The patients exhibited loss of rod vision more severe than cone vision. Funduscopic images showed widespread retinal degeneration with pigment clumping, optic disk pallor, arteriole attenuation, and a peri-foveal ring of hyper autofluorescence. Three families were tested for olfactory dysfunction and results indicated mild to complete anosmia in individuals with mutations in . Genetic analysis revealed 6 novel variants, c.2127 C > G, p.Phe709Leu; c.1431 C > A, p.Cys477*; c.2034 G > A, p.Trp678*; c.2092 T > C, p.Cys698Arg; and c.583 + 2 T > C, c.2305-34 G > A and 3 variants that have been previously described, c.2957A>T, p.Asn986Ile; c.2544dup, p.Leu849Alafs*3; and c.2492 + 1 G > A.

DISCUSSION

This is the first report for six novel variants associated with arRP. Two families had olfactory dysfunction in patients with arRP and family members who were heterozygous for a mutation. Additionally, findings demonstrated variable penetrance and expressivity of disease in these patients.