ClinVar

In a consanguineous Indian family (PMK30) in which 4 individuals had autosomal recessive childhood-onset severe retinal dystrophy, Gu et al. (1997) mapped the disease locus, which they designated RP20 (613794), to chromosome 1p31-p22. Gu et al. (1997) found that all 4 affected individuals were homozygous for a 1141C-A transversion in the RPE65 gene. The 4 parents were heterozygous for the sequence change, as were 3 of the 4 unaffected sibs; the fourth unaffected sib carried only the wildtype sequence. The mutation predicted a nonconservative replacement of the evolutionarily conserved proline-363 by threonine (P363T). The onset of severe visual impairment in this family varied between 3 and 7 years of age. Night blindness was a typical and early symptom in all patients. Most patients became severely visually handicapped between 5 and 12 years of age and could only count fingers at 1 to 3 meters distance or were able to see only hand movements. The 4 patients varied in age from 20 to 32 years. Two had nystagmus, which was consistent with an early onset of severe visual disability. Fundus examination showed attenuated vessels and atrophy of the optic disc. Although bone-spicule formation was not a typical feature, many whitish dots were compatible with extensive RPE defects.