Publication Date:
2014-10-09
Description:
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.
Print ISSN:
0964-6906
Electronic ISSN:
1460-2083
Topics:
Biology
,
Medicine
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