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Identification of a novel protein truncating mutation p.Asp98* in XPC associated with xeroderma pigmentosum in a consanguineous Pakistani family

BACKGROUND: Xeroderma pigmentosum (XP) is a rare genetic disorder, which is characterized by hyper‐sensitivity to solar ultraviolet (UV) radiation. Clinical consequences of sun exposure are skin lesions and an increased risk of developing skin cancer. Genetic studies have identified eight genes asso...

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Autores principales: Ali, Muhammad Z., Blatterer, Jasmin, Khan, Muzammil A., Schaflinger, Erich, Petek, Erwin, Ahmad, Safeer, Khan, Ejazullah, Windpassinger, Christian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7005610/
https://www.ncbi.nlm.nih.gov/pubmed/31923348
http://dx.doi.org/10.1002/mgg3.1060
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author Ali, Muhammad Z.
Blatterer, Jasmin
Khan, Muzammil A.
Schaflinger, Erich
Petek, Erwin
Ahmad, Safeer
Khan, Ejazullah
Windpassinger, Christian
author_facet Ali, Muhammad Z.
Blatterer, Jasmin
Khan, Muzammil A.
Schaflinger, Erich
Petek, Erwin
Ahmad, Safeer
Khan, Ejazullah
Windpassinger, Christian
author_sort Ali, Muhammad Z.
collection PubMed
description BACKGROUND: Xeroderma pigmentosum (XP) is a rare genetic disorder, which is characterized by hyper‐sensitivity to solar ultraviolet (UV) radiation. Clinical consequences of sun exposure are skin lesions and an increased risk of developing skin cancer. Genetic studies have identified eight genes associated with xeroderma pigmentosum. The proteins encoded by these genes are mainly involved in DNA repair mechanisms. METHODS: Molecular genetic characterization of patients with xeroderma pigmentosum involved positional cloning methods such as homozygosity mapping and subsequent candidate gene analysis. Mutation screening was performed through Sanger DNA sequencing. RESULTS AND DISCUSSION: In this case study, we report a novel protein truncating mutation in XPC associated with autosomal recessive xeroderma pigmentosum in a consanguineous Pakistani family. Genetic mapping revealed a novel single base insertion of a thymine nucleotide NM_004628.4: c.291dupT (c.291_292insT) in the second exon of XPC. The identified mutation leads to a premature stop codon (TGA) at amino acid position 98 (p.Asp98*) and thus presumably results in a truncated protein. The Xeroderma pigmentosum, complementation group C (XPC) is located on 3p25.1 and encodes a protein involved in nucleotide excision repair. The identified mutation presumably truncates all functional domains of the XPC protein, which likely results in the loss of protein function. CONCLUSION: The study expands the knowledge of the mutational spectrum of XPC and is valuable for genetic counseling of affected individuals and their families.
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spelling pubmed-70056102020-02-13 Identification of a novel protein truncating mutation p.Asp98* in XPC associated with xeroderma pigmentosum in a consanguineous Pakistani family Ali, Muhammad Z. Blatterer, Jasmin Khan, Muzammil A. Schaflinger, Erich Petek, Erwin Ahmad, Safeer Khan, Ejazullah Windpassinger, Christian Mol Genet Genomic Med Original Articles BACKGROUND: Xeroderma pigmentosum (XP) is a rare genetic disorder, which is characterized by hyper‐sensitivity to solar ultraviolet (UV) radiation. Clinical consequences of sun exposure are skin lesions and an increased risk of developing skin cancer. Genetic studies have identified eight genes associated with xeroderma pigmentosum. The proteins encoded by these genes are mainly involved in DNA repair mechanisms. METHODS: Molecular genetic characterization of patients with xeroderma pigmentosum involved positional cloning methods such as homozygosity mapping and subsequent candidate gene analysis. Mutation screening was performed through Sanger DNA sequencing. RESULTS AND DISCUSSION: In this case study, we report a novel protein truncating mutation in XPC associated with autosomal recessive xeroderma pigmentosum in a consanguineous Pakistani family. Genetic mapping revealed a novel single base insertion of a thymine nucleotide NM_004628.4: c.291dupT (c.291_292insT) in the second exon of XPC. The identified mutation leads to a premature stop codon (TGA) at amino acid position 98 (p.Asp98*) and thus presumably results in a truncated protein. The Xeroderma pigmentosum, complementation group C (XPC) is located on 3p25.1 and encodes a protein involved in nucleotide excision repair. The identified mutation presumably truncates all functional domains of the XPC protein, which likely results in the loss of protein function. CONCLUSION: The study expands the knowledge of the mutational spectrum of XPC and is valuable for genetic counseling of affected individuals and their families. John Wiley and Sons Inc. 2020-01-10 /pmc/articles/PMC7005610/ /pubmed/31923348 http://dx.doi.org/10.1002/mgg3.1060 Text en © 2019 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Ali, Muhammad Z.
Blatterer, Jasmin
Khan, Muzammil A.
Schaflinger, Erich
Petek, Erwin
Ahmad, Safeer
Khan, Ejazullah
Windpassinger, Christian
Identification of a novel protein truncating mutation p.Asp98* in XPC associated with xeroderma pigmentosum in a consanguineous Pakistani family
title Identification of a novel protein truncating mutation p.Asp98* in XPC associated with xeroderma pigmentosum in a consanguineous Pakistani family
title_full Identification of a novel protein truncating mutation p.Asp98* in XPC associated with xeroderma pigmentosum in a consanguineous Pakistani family
title_fullStr Identification of a novel protein truncating mutation p.Asp98* in XPC associated with xeroderma pigmentosum in a consanguineous Pakistani family
title_full_unstemmed Identification of a novel protein truncating mutation p.Asp98* in XPC associated with xeroderma pigmentosum in a consanguineous Pakistani family
title_short Identification of a novel protein truncating mutation p.Asp98* in XPC associated with xeroderma pigmentosum in a consanguineous Pakistani family
title_sort identification of a novel protein truncating mutation p.asp98* in xpc associated with xeroderma pigmentosum in a consanguineous pakistani family
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7005610/
https://www.ncbi.nlm.nih.gov/pubmed/31923348
http://dx.doi.org/10.1002/mgg3.1060
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