Mutations in SNRPE, which encodes a core protein of the spliceosome, cause autosomal-dominant hypotrichosis simplex

Pasternack, S.M., Refke, M., Paknia, E., Hennies, Hans C., Franz, T., Schäfer, N., Fryer, A., van Steensel, M., Sweeney, E., Just, M., Grimm, C., Kruse, R., Ferrandiz, C., Nöthen, M.M., Fischer, U. and Betz, R.C. (2013) Mutations in SNRPE, which encodes a core protein of the spliceosome, cause autosomal-dominant hypotrichosis simplex. The American Journal of Human Genetics, 92 (1). pp. 81-87. ISSN 0002-9297

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Abstract

Hypotrichosis simplex (HS) comprises a group of hereditary isolated alopecias that are characterized by a diffuse and progressive loss of hair starting in childhood and shows a wide phenotypic variability. We mapped an autosomal-dominant form of HS to chromosome 1q31.3-1q41 in a Spanish family. By direct sequencing, we identified the heterozygous mutation c.1A>G (p.Met1?) in SNRPE that results in loss of the start codon of the transcript. We identified the same mutation in a simplex HS case from the UK and an additional mutation (c.133G>A [p.Gly45Ser]) in a simplex HS case originating from Tunisia. SNRPE encodes a core protein of U snRNPs, the key factors of the pre-mRNA processing spliceosome. The missense mutation c.133G>A leads to a glycine to serine substitution and is predicted to disrupt the structure of SNRPE. Western blot analyses of HEK293T cells expressing SNRPE c.1A>G revealed an N-terminally truncated protein, and therefore the mutation might result in use of an alternative in-frame downstream start codon. Subcellular localization of mutant SNRPE by immunofluorescence analyses as well as incorporation of mutant SNRPE proteins into U snRNPs was found to be normal, suggesting that the function of U snRNPs in splicing, rather than their biogenesis, is affected. In this report we link a core component of the spliceosome to hair loss, thus adding another specific factor in the complexity of hair growth. Furthermore, our findings extend the range of human phenotypes that are linked to the splicing machinery.

Item Type:	Article
Additional Information:	Unmapped bibliographic data: ST - Mutations in SNRPE, which encodes a core protein of the spliceosome, cause autosomal-dominant hypotrichosis simplex [Field not mapped to EPrints] C2 - PMC3542472 [Field not mapped to EPrints] AD - Institute of Human Genetics, University of Bonn, 53127 Bonn, Germany. [Field not mapped to EPrints] AN - 23246290 [Field not mapped to EPrints]
Uncontrolled Keywords:	Female
Subjects:	Q Science > QH Natural history > QH301 Biology Q Science > QH Natural history > QH426 Genetics
Schools:	School of Applied Sciences
Depositing User:	Hans Hennies
Date Deposited:	06 Jul 2016 15:29
Last Modified:	01 Apr 2018 18:30
URI:	http://eprints.hud.ac.uk/id/eprint/28766

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