title: 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.affiliation: Department of Ophthalmology.
authors.forename: Yajing Angela
authors.initials: YA
authors.lastname: Xie
authors.affiliation: Department of Ophthalmology.
authors.forename: Winston
authors.initials: W
authors.lastname: Lee
authors.affiliation: Department of Ophthalmology.
authors.forename: Carolyn
authors.initials: C
authors.lastname: Cai
authors.affiliation: Department of Molecular and Human Genetics.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Gambin
authors.affiliation: Department of Ophthalmology.
authors.forename: Kalev
authors.initials: K
authors.lastname: Nõupuu
authors.affiliation: Department of Ophthalmology.
authors.forename: Tharikarn
authors.initials: T
authors.lastname: Sujirakul
authors.affiliation: 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.
authors.forename: Carmen
authors.initials: C
authors.lastname: Ayuso
authors.affiliation: Department of Molecular and Human Genetics.
authors.forename: Shalini
authors.initials: S
authors.lastname: Jhangiani
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Donna
authors.initials: D
authors.lastname: Muzny
authors.affiliation: Department of Molecular and Human Genetics.
authors.forename: Eric
authors.initials: E
authors.lastname: Boerwinkle
authors.affiliation: Department of Molecular and Human Genetics, Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Gibbs
authors.affiliation: Department of Ophthalmology.
authors.forename: Vivienne C
authors.initials: VC
authors.lastname: Greenstein
authors.affiliation: Department of Molecular and Human Genetics, Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: James R
authors.initials: JR
authors.lastname: Lupski
authors.affiliation: Department of Ophthalmology, Department of Pathology and Cell Biology, Columbia University, New York, NY 10032, USA.
authors.forename: Stephen H
authors.initials: SH
authors.lastname: Tsang
authors.affiliation: Department of Ophthalmology, Department of Pathology and Cell Biology, Columbia University, New York, NY 10032, USA, rla22@columbia.edu.
authors.forename: Rando
authors.initials: R
authors.lastname: Allikmets
mesh_terms: D000293:Adolescent; D002648:Child; D018389:Codon, Nonsense; D005260:Female; D006801:Humans; D008297:Male; D010088:Oxidoreductases / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D012174:Retinitis Pigmentosa / Q000175:diagnosis / Q000235:genetics*; D013577:Syndrome; D014787:Vision Tests; D014792:Visual Acuity; D055815:Young Adult
chemical_list: D018389:Codon, Nonsense; D010088:Oxidoreductases; C422653:RDH11 protein, human