New syndrome with retinitis pigmentosa is caused by nonsense mutations in retinol dehydrogenase RDH11.

 
TitleNew syndrome with retinitis pigmentosa is caused by nonsense mutations in retinol dehydrogenase RDH11.
Publication TypeJournal Article
Year of Publication2014
AuthorsXie, YAngela, Lee, W, Cai, C, Gambin, T, Nõupuu, K, Sujirakul, T, Ayuso, C, Jhangiani, S, Muzny, DM, Boerwinkle, E, Gibbs, RA, Greenstein, VC, Lupski, JR, Tsang, SH, Allikmets, R
JournalHum Mol Genet
Volume23
Issue21
Pagination5774-80
Date Published2014 Nov 1
ISSN1460-2083
KeywordsAdolescent, Child, Codon, Nonsense, Female, Humans, Male, Oxidoreductases, Pedigree, Phenotype, Retinitis Pigmentosa, Syndrome, Vision Tests, Visual Acuity, Young Adult
Abstract

Retinitis pigmentosa (RP), a genetically heterogeneous group of retinopathies that occur in both non-syndromic and syndromic forms, is caused by mutations in ∼100 genes. Although recent advances in next-generation sequencing have aided in the discovery of novel RP genes, a number of the underlying contributing genes and loci remain to be identified. We investigated three siblings, born to asymptomatic parents of Italian-American descent, who each presented with atypical RP with systemic features, including facial dysmorphologies, psychomotor developmental delays recognized since early childhood, learning disabilities and short stature. RP-associated ophthalmological findings included salt-and-pepper retinopathy, attenuation of the arterioles and generalized rod-cone dysfunction as determined by almost extinguished electroretinogram in 2 of 3 siblings. Atypical for RP features included mottled macula at an early age and peripapillary sparing of the retinal pigment epithelium. Whole-exome sequencing data, queried under a recessive model of inheritance, identified compound heterozygous stop mutations, c.C199T:p.R67* and c.C322T:p.R108*, in the retinol dehydrogenase 11 (RDH11) gene, resulting in a non-functional protein, in all affected children. In summary, deleterious mutations in RDH11, an important enzyme for vision-related and systemic retinoic acid metabolism, cause a new syndrome with RP.

DOI10.1093/hmg/ddu291
Alternate JournalHum. Mol. Genet.
PubMed ID24916380
PubMed Central IDPMC4189905
Grant ListR01 EY018213 / EY / NEI NIH HHS / United States
U54 HG006542 / HG / NHGRI NIH HHS / United States
R01 EY009076 / EY / NEI NIH HHS / United States
U54 HD083092 / HD / NICHD NIH HHS / United States
R24 EY019861 / EY / NEI NIH HHS / United States
HG006542 / HG / NHGRI NIH HHS / United States
EY019007 / EY / NEI NIH HHS / United States
EY021163 / EY / NEI NIH HHS / United States
R01 EY021163 / EY / NEI NIH HHS / United States
EY019861 / EY / NEI NIH HHS / United States