title: Mutations in c10orf11, a melanocyte-differentiation gene, cause autosomal-recessive albinism.
abstract: Autosomal-recessive albinism is a hypopigmentation disorder with a broad phenotypic range. A substantial fraction of individuals with albinism remain genetically unresolved, and it has been hypothesized that more genes are to be identified. By using homozygosity mapping of an inbred Faroese family, we identified a 3.5 Mb homozygous region (10q22.2-q22.3) on chromosome 10. The region contains five protein-coding genes, and sequencing of one of these, C10orf11, revealed a nonsense mutation that segregated with the disease and showed a recessive inheritance pattern. Investigation of additional albinism-affected individuals from the Faroe Islands revealed that five out of eight unrelated affected persons had the nonsense mutation in C10orf11. Screening of a cohort of autosomal-recessive-albinism-affected individuals residing in Denmark showed a homozygous 1 bp duplication in C10orf11 in an individual originating from Lithuania. Immunohistochemistry showed localization of C10orf11 in melanoblasts and melanocytes in human fetal tissue, but no localization was seen in retinal pigment epithelial cells. Knockdown of the zebrafish (Danio rerio) homolog with the use of morpholinos resulted in substantially decreased pigmentation and a reduction of the apparent number of pigmented melanocytes. The morphant phenotype was rescued by wild-type C10orf11, but not by mutant C10orf11. In conclusion, we have identified a melanocyte-differentiation gene, C10orf11, which when mutated causes autosomal-recessive albinism in humans.
authors: Applied Human Molecular Genetics, Kennedy Center, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark. karen.groenskov@regionh.dk
authors: Karen
authors: K
authors: Grønskov
authors: Christopher M
authors: CM
authors: Dooley
authors: Elsebet
authors: E
authors: Østergaard
authors: Robert N
authors: RN
authors: Kelsh
authors: Lars
authors: L
authors: Hansen
authors: Mitchell P
authors: MP
authors: Levesque
authors: Kaj
authors: K
authors: Vilhelmsen
authors: Kjeld
authors: K
authors: Møllgård
authors: Derek L
authors: DL
authors: Stemple
authors: Thomas
authors: T
authors: Rosenberg
mesh_terms: D000417:Albinism / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D002869:Chromosome Aberrations; D002874:Chromosome Mapping / Q000379:methods; D002879:Chromosomes, Human, Pair 10; D018389:Codon, Nonsense; D005260:Female; D005808:Genes, Recessive; D020022:Genetic Predisposition to Disease; D006720:Homozygote; D006801:Humans; D008297:Male; D008544:Melanocytes / Q000378:metabolism* / Q000473:pathology; D010858:Pigmentation / Q000235:genetics; D055213:Retinal Pigment Epithelium / Q000378:metabolism; D015027:Zebrafish
chemical_list: D018389:Codon, Nonsense
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