Mutations in C10orf11, a Melanocyte-Differentiation Gene, Cause Autosomal-Recessive Albinism
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,...
Published in: | The American Journal of Human Genetics |
---|---|
Main Authors: | , , , , , , , , , |
Format: | Text |
Language: | English |
Published: |
Elsevier
2013
|
Subjects: | |
Online Access: | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3591853 http://www.ncbi.nlm.nih.gov/pubmed/23395477 https://doi.org/10.1016/j.ajhg.2013.01.006 |
id |
ftpubmed:oai:pubmedcentral.nih.gov:3591853 |
---|---|
record_format |
openpolar |
spelling |
ftpubmed:oai:pubmedcentral.nih.gov:3591853 2023-05-15T16:10:53+02:00 Mutations in C10orf11, a Melanocyte-Differentiation Gene, Cause Autosomal-Recessive Albinism Grønskov, Karen Dooley, Christopher M. Østergaard, Elsebet Kelsh, Robert N. Hansen, Lars Levesque, Mitchell P. Vilhelmsen, Kaj Møllgård, Kjeld Stemple, Derek L. Rosenberg, Thomas 2013-03-07 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3591853 http://www.ncbi.nlm.nih.gov/pubmed/23395477 https://doi.org/10.1016/j.ajhg.2013.01.006 en eng Elsevier http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3591853 http://www.ncbi.nlm.nih.gov/pubmed/23395477 http://dx.doi.org/10.1016/j.ajhg.2013.01.006 © 2013 The American Society of Human Genetics. Published by Elsevier Ltd. All right reserved. Report Text 2013 ftpubmed https://doi.org/10.1016/j.ajhg.2013.01.006 2013-09-15T00:21:51Z 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. Text Faroe Islands PubMed Central (PMC) Faroe Islands The American Journal of Human Genetics 92 3 415 421 |
institution |
Open Polar |
collection |
PubMed Central (PMC) |
op_collection_id |
ftpubmed |
language |
English |
topic |
Report |
spellingShingle |
Report Grønskov, Karen Dooley, Christopher M. Østergaard, Elsebet Kelsh, Robert N. Hansen, Lars Levesque, Mitchell P. Vilhelmsen, Kaj Møllgård, Kjeld Stemple, Derek L. Rosenberg, Thomas Mutations in C10orf11, a Melanocyte-Differentiation Gene, Cause Autosomal-Recessive Albinism |
topic_facet |
Report |
description |
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. |
format |
Text |
author |
Grønskov, Karen Dooley, Christopher M. Østergaard, Elsebet Kelsh, Robert N. Hansen, Lars Levesque, Mitchell P. Vilhelmsen, Kaj Møllgård, Kjeld Stemple, Derek L. Rosenberg, Thomas |
author_facet |
Grønskov, Karen Dooley, Christopher M. Østergaard, Elsebet Kelsh, Robert N. Hansen, Lars Levesque, Mitchell P. Vilhelmsen, Kaj Møllgård, Kjeld Stemple, Derek L. Rosenberg, Thomas |
author_sort |
Grønskov, Karen |
title |
Mutations in C10orf11, a Melanocyte-Differentiation Gene, Cause Autosomal-Recessive Albinism |
title_short |
Mutations in C10orf11, a Melanocyte-Differentiation Gene, Cause Autosomal-Recessive Albinism |
title_full |
Mutations in C10orf11, a Melanocyte-Differentiation Gene, Cause Autosomal-Recessive Albinism |
title_fullStr |
Mutations in C10orf11, a Melanocyte-Differentiation Gene, Cause Autosomal-Recessive Albinism |
title_full_unstemmed |
Mutations in C10orf11, a Melanocyte-Differentiation Gene, Cause Autosomal-Recessive Albinism |
title_sort |
mutations in c10orf11, a melanocyte-differentiation gene, cause autosomal-recessive albinism |
publisher |
Elsevier |
publishDate |
2013 |
url |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3591853 http://www.ncbi.nlm.nih.gov/pubmed/23395477 https://doi.org/10.1016/j.ajhg.2013.01.006 |
geographic |
Faroe Islands |
geographic_facet |
Faroe Islands |
genre |
Faroe Islands |
genre_facet |
Faroe Islands |
op_relation |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3591853 http://www.ncbi.nlm.nih.gov/pubmed/23395477 http://dx.doi.org/10.1016/j.ajhg.2013.01.006 |
op_rights |
© 2013 The American Society of Human Genetics. Published by Elsevier Ltd. All right reserved. |
op_doi |
https://doi.org/10.1016/j.ajhg.2013.01.006 |
container_title |
The American Journal of Human Genetics |
container_volume |
92 |
container_issue |
3 |
container_start_page |
415 |
op_container_end_page |
421 |
_version_ |
1765996014251016192 |