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

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.

• Authors: Yajing Angela Xie, Winston Lee, Carolyn Cai, Tomasz Gambin, Kalev Nõupuu, Tharikarn Sujirakul, Carmen Ayuso, Shalini Jhangiani, Donna Muzny, Eric Boerwinkle, Richard Gibbs, Vivienne C Greenstein, James R Lupski, Stephen H Tsang, Rando Allikmets
• Journal: Human molecular genetics (Hum Mol Genet) Vol. 23 Issue 21 Pg. 5774-80 (Nov 01 2014) ISSN: 1460-2083 [Electronic] England
• PMID: 24916380 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: [email protected].

Chemical References

• Codon, Nonsense
• Oxidoreductases
• RDH11 protein, human

Topics

• Adolescent
• Child
• Codon, Nonsense
• Female
• Humans
• Male
• Oxidoreductases (genetics)
• Pedigree
• Phenotype
• Retinitis Pigmentosa (diagnosis, genetics)
• Syndrome
• Vision Tests
• Visual Acuity
• Young Adult