This variant is classified as a variant of unknown significance because its contribution to retinitis pigmentosa (RP; see 268000) has not been confirmed.
In a 19-year-old woman of Moroccan/Yemenite Jewish descent with short stature, severe microcephaly, and RP, who was negative for chromosomal microdeletions/duplications and Moroccan and Yemenite Jewish RP founder mutations, Weisz Hubshman et al. (2018) identified homozygosity for a 2-bp deletion (c.304_305delGA, NM_0010992271) in the POC5 gene, resulting in a premature termination codon (asp102 to ter, D102X). Her unaffected parents and brother were heterozygous for the mutation. The proband wore glasses from age 6 years due to myopia, and later a mild central posterior subcapsular/polar cataract was detected. At age 14, she was diagnosed with RP, at which time full-field electroretinography revealed nondetectable rod responses with cone responses reduced but still present. Visual acuity at age 19 was 20/40, and visual fields were constricted to 10 to 20 degrees from fixation. Funduscopy showed salt and pepper-like hyperpigmentation in the midperiphery, with early bone spicule-like pigmentary changes, mild optic disc pallor, and mild attenuation of retinal vessels. Fundus autofluorescence images showed hyperfluorescence in the macular region with hypofluorescent areas throughout the more peripheral retina. Optical coherence tomography scans showed thinning and loss of the photoreceptor outer nuclear layer in extrafoveal regions. The proband also experienced recurrent episodes of glomerulonephritis, with focal segmental glomerulonephritis on 1 biopsy and immunoglobulin A nephropathy on another. In addition, she had recurrent episodes of muscle pain/cramps, associated with elevated creatine phosphokinase.
