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