Mutations in C10orf11, a melanocyte-differentiation gene, cause autosomal-recessive albinism

K. Gronskov, C. M. Dooley, E. Ostergaard, Robert N. Kelsh, L. Hansen, M. P. Levesque, K. Vilhelmsen, K. Mollgard, D. Stemple, T. Rosenberg

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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.
Original languageEnglish
Pages (from-to)415-421
Number of pages7
JournalAmerican Journal of Human Genetics
Volume92
Issue number3
Early online date7 Feb 2013
DOIs
Publication statusPublished - 7 Mar 2013

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Albinism
Melanocytes
Mutation
Nonsense Codon
Genes
Zebrafish
Denmark
Lithuania
Hypopigmentation
Morpholinos
Inheritance Patterns
Chromosomes, Human, Pair 10
Retinal Pigments
Pigmentation
Fetus
Epithelial Cells
Immunohistochemistry
Phenotype
Proteins

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Mutations in C10orf11, a melanocyte-differentiation gene, cause autosomal-recessive albinism. / Gronskov, K.; Dooley, C. M.; Ostergaard, E.; Kelsh, Robert N.; Hansen, L.; Levesque, M. P.; Vilhelmsen, K.; Mollgard, K.; Stemple, D.; Rosenberg, T.

In: American Journal of Human Genetics, Vol. 92, No. 3, 07.03.2013, p. 415-421.

Research output: Contribution to journalArticle

Gronskov, K, Dooley, CM, Ostergaard, E, Kelsh, RN, Hansen, L, Levesque, MP, Vilhelmsen, K, Mollgard, K, Stemple, D & Rosenberg, T 2013, 'Mutations in C10orf11, a melanocyte-differentiation gene, cause autosomal-recessive albinism', American Journal of Human Genetics, vol. 92, no. 3, pp. 415-421. https://doi.org/10.1016/j.ajhg.2013.01.006
Gronskov, K. ; Dooley, C. M. ; Ostergaard, E. ; Kelsh, Robert N. ; Hansen, L. ; Levesque, M. P. ; Vilhelmsen, K. ; Mollgard, K. ; Stemple, D. ; Rosenberg, T. / Mutations in C10orf11, a melanocyte-differentiation gene, cause autosomal-recessive albinism. In: American Journal of Human Genetics. 2013 ; Vol. 92, No. 3. pp. 415-421.
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AU - Hansen, L.

AU - Levesque, M. P.

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