Retinitis Pigmentosa 81

A number sign (#) is used with this entry because of evidence that retinitis pigmentosa-81 (RP81) is caused by homozygous mutation in the IFT43 gene (614068) on chromosome 14q24. One such family has been reported.

For a general phenotypic description and a discussion of genetic heterogeneity of retinitis pigmentosa, see 268000.

Clinical Features

Biswas et al. (2017) studied a large consanguineous Pakistani family (PKRD272) in which 9 members exhibited early-onset retinal degeneration. The 4 affected sibs (patients III:1, III:2, III:7, and III:8) who underwent clinical analysis all reported noticeable night vision abnormalities before age 5 years. Funduscopy in 2 of the sibs (III:1 and III:8) at ages 30 and 23 years, respectively, showed optic nerve pallor, retinal vessel attenuation, and bone spicule pigmentary changes anterior to the arcades and in the nasal retina. Both sibs showed atrophy of the retinal pigment epithelium and choroid in the macula, which was more extensive in the older sib. Full-field electroretinography (ERG) responses were undetectable to all stimulus conditions in all 4 sibs at ages ranging from 28 to 46 years, whereas an unaffected sib showed normal cone and rod responses at age 30 years. The affected sibs had normal physical development and body mass index, and exhibited no features of Sensenbrenner syndrome (see CED3, 614099) such as polydactyly, short ribs, or micromelia.

Mapping

In 4 affected and 2 unaffected individuals from a large consanguineous Pakistani family (PKRD272) with early-onset retinal degeneration, Biswas et al. (2017) performed homozygosity mapping and identified an 18-Mb homozygous region on chromosome 14 (chr14:59,000,001-77,000,000) that was shared by the 4 affected sibs. The interval contained 3 known retinal disease-associated genes (RDH11, 607849; RDH12, 608830; TTLL5, 612268), but no pathogenic variants were detected in those genes that segregated with disease in the family.

Molecular Genetics

In 4 affected individuals from a large consanguineous Pakistani family (PKRD272) with early-onset retinal degeneration mapping to chromosome 14, Biswas et al. (2017) analyzed exome sequencing data and identified homozygosity for a missense mutation in the IFT43 gene (E34K; 614068.0004), located within an 18-Mb shared region of homozygosity and segregating fully with disease in the family. The mutation was not found in 150 ethnicity-matched controls or in 800 other controls, and screening whole-exome or whole-genome data from 1,771 and 120 patients, respectively, from pedigrees with inherited retinal diseases did not identify any additional mutations in the IFT43 gene. The authors concluded that IFT43-associated retinal disease is uncommon.