A number sign (#) is used with this entry because of evidence that retinitis pigmentosa-98 (RP98) is caused by homozygous or compound heterozygous mutation in the TMEM216 gene (613277) on chromosome 11q12.

Retinitis pigmentosa (RP98) is an autosomal recessive disorder characterized by onset of night blindness in early childhood, with gradual loss of peripheral vision and later of central vision (Malka et al., 2024).

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

Malka et al. (2024) reported 45 patients from 40 families of African ancestry and 29 patients from 9 families of South Asian ancestry with nonsyndromic retinitis pigmentosa and mutation in the TMEM216 gene. Detailed clinical data were available for 31 patients, all of whom experienced night blindness in the first decade of life, with progressive loss of peripheral field vision over subsequent years and loss of visual acuity starting in the third decade. OCT and en face images were typical for RP, with primary loss of rod photoreceptor structures and secondary loss of the cone-rich central macula and fovea. Electroretinography showed abrogated responses to both rod and cone stimuli, with even children under 10 years of age having barely detectable cone-driven and undetectable rod-driven responses. None of the patients (age range at examination, 5-72 years) exhibited systemic features suggestive of generalized ciliopathy. There was no difference between the 2 cohorts in terms of age of onset or progression of disease.

The transmission pattern of retinitis pigmentosa in the families reported by Malka et al. (2024) was consistent with autosomal recessive inheritance.

In 71 patients from 47 families of African or South Asian ancestry with nonsyndromic retinitis pigmentosa, who were negative for mutation in known retinal dystrophy-associated genes, Malka et al. (2024) identified homozygosity for 2 different nucleotide substitutions at the same genomic location, noncoding variants located 69 basepairs upstream of the TMEM216 start codon: in the patients of African ancestry, the mutation was a c.-69G-T transversion (613277.0005) and in the patients of South Asian ancestry, the mutation was a c.-69G-A transition (613277.0006). In 2 additional families of African ancestry, compound heterozygosity for the c.-69G-T variant and another mutation was present: in 2 affected brothers from Zimbabwe, the second mutation was a large deletion that included exons 1 to 3 of TMEM216, and in a female patient from the Caribbean, the mutation in trans was a splice site variant (613277.0007). Both recurrent variants were found in the gnomAD database, with enrichment in the African and South Asian populations, respectively. Haplotype analysis in both cohorts revealed a conserved haplotype that strongly suggested a single founder mutation unique to each group.