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

作者：Xie Yajing; Lee Winston; Cai Carolyn; Gambin Tomasz; Noupuu Kalev; Sujirakul Tharikarn; Ayuso Carmen; Jhangiani Shalini; Muzny Donna; Boerwinkle Eric; Gibbs Richard; Greenstein Vivienne C; Lupski James R; Tsang Stephen H; Allikmets Rando^*

来源：Human Molecular Genetics, 2014, 23(21): 5774-5780.

DOI：10.1093/hmg/ddu291

Retinitis pigmentosa (RP), a genetically heterogeneous group of retinopathies that occur in both non-syndromic and syndromic forms, is caused by mutations in similar to 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.

• 出版日期2014-11-1