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Hum Mol Genet. 2014 Nov 1;23(21):5774-80. doi: 10.1093/hmg/ddu291. Epub 2014 Jun 10.

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

Author information

1
Department of Ophthalmology.
2
Department of Molecular and Human Genetics.
3
Department of Genetics, Instituto de Investigacion Sanitaria-University Hospital Fundacion Jimenez Diaz (IIS-FJD), Madrid, 28040 Spain and Centro de Investigacion Biomedica en Red (CIBER) de Enfermedades Raras, ISCIII, Madrid, 28040 Spain.
4
Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA.
5
Department of Molecular and Human Genetics, Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA.
6
Department of Ophthalmology, Department of Pathology and Cell Biology, Columbia University, New York, NY 10032, USA.
7
Department of Ophthalmology, Department of Pathology and Cell Biology, Columbia University, New York, NY 10032, USA, rla22@columbia.edu.

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.

PMID:
24916380
PMCID:
PMC4189905
DOI:
10.1093/hmg/ddu291
[Indexed for MEDLINE]
Free PMC Article

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