Retinitis Pigmentosa 72
A number sign (#) is used with this entry because of evidence that retinitis pigmentosa-72 (RP72) is caused by homozygous mutation in the ZNF408 gene (616454) on chromosome 11p11.
Heterozygous mutation in the ZNF408 gene has been reported to cause exudative vitreoretinopathy (see EVR6, 616468).
For a general phenotypic description and discussion of genetic heterogeneity of retinitis pigmentosa (RP), see 268000.
Clinical FeaturesAvila-Fernandez et al. (2015) studied 3 patients from 2 unrelated Spanish families who presented with night blindness followed by visual field loss and decreased visual acuity. Two sisters, born of unaffected parents from the same small geographic area, had onset of symptoms at 30 and 40 years of age, whereas the unrelated male patient from a consanguineous family presented at 17 years of age. The reductions in visual fields ranged from 30 degrees to 10 degrees and were symmetric; best-corrected visual acuities ranged from 20/25 to 20/40. Visualization of fundi was blurred in all 3 patients due to vitreous condensations, but showed typical changes of RP with pale optic discs, narrowed vessels, and bone-spicule pigmentation.
Molecular GeneticsIn 2 Spanish sisters with RP and minor vitreous abnormalities, 1 of whom was known to be negative for mutation in all autosomal recessive RP (arRP)-associated genes, Avila-Fernandez et al. (2015) performed homozygosity mapping followed by exome sequencing and identified homozygosity for a 2-bp deletion in the ZNF408 gene (616454.0003). The mutation was not found in 374 ethnically matched alleles or in the 1000 Genomes Project or Exome Variant Server databases. The unaffected parents were both deceased. Sequencing the ZNF408 gene in 217 additional Spanish probands with sporadic RP or arRP revealed homozygosity for a missense mutation (R541C; 616454.0004) in a 50-year-old man born of consanguineous parents. His unaffected son and daughter were both heterozygous for R541C; no retinal vasculature abnormalities were observed by funduscopic examination, fluorescein angiography, or optical coherence tomography (OCT). In 2 other probands, 2 heterozygous missense variants (G492R and Q583K) in ZNF408 were identified; these changes, which involved highly conserved residues, were not found in 75 in-house exomes. No second mutation or copy number variation was detected in DNA from these 2 patients, who were not available for further ophthalmologic examination.