{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2022,4,2]],"date-time":"2022-04-02T23:16:40Z","timestamp":1648941400617},"reference-count":30,"publisher":"Springer Science and Business Media LLC","issue":"1","content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Biomed Sci"],"published-print":{"date-parts":[[2013,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Xeroderma Pigmentosum (XP) is a rare skin disorder characterized by skin hypersensitivity to sunlight and abnormal pigmentation. The aim of this study was to investigate the genetic cause of a severe XP phenotype in a consanguineous Pakistani family and <jats:italic>in silico<\/jats:italic> characterization of any identified disease-associated mutation.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>The XP complementation group was assigned by genotyping of family for known XP loci. Genotyping data mapped the family to complementation group A locus, involving <jats:italic>XPA<\/jats:italic> gene. Mutation analysis of the candidate XP gene by DNA sequencing revealed a novel deletion mutation <jats:italic>(c.654del A)<\/jats:italic> in exon 5 of <jats:italic>XPA<\/jats:italic> gene. The c.654del A, causes frameshift, which pre-maturely terminates protein and result into a truncated product of 222 amino acid (aa) residues instead of 273 <jats:italic>(p.Lys218AsnfsX5)<\/jats:italic>. In silico tools were applied to study the likelihood of changes in structural motifs and thus interaction of mutated protein with binding partners. <jats:italic>In silico<\/jats:italic> analysis of mutant protein sequence, predicted to affect the aa residue which attains coiled coil structure. The coiled coil structure has an important role in key cellular interactions, especially with DNA damage-binding protein 2 (DDB2), which has important role in DDB-mediated nucleotide excision repair (NER) system.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>Our findings support the fact of genetic and clinical heterogeneity in XP. The study also predicts the critical role of DDB2 binding region of XPA protein in NER pathway and opens an avenue for further research to study the functional role of the mutated protein domain.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1423-0127-20-70","type":"journal-article","created":{"date-parts":[[2013,9,25]],"date-time":"2013-09-25T03:28:15Z","timestamp":1380079695000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["In silico characterization of a novel pathogenic deletion mutation identified in XPA gene in a Pakistani family with severe xeroderma pigmentosum"],"prefix":"10.1186","volume":"20","author":[{"given":"Muhammad","family":"Nasir","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nafees","family":"Ahmad","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian MK","family":"Sieber","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amir","family":"Latif","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Salman Akbar","family":"Malik","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abdul","family":"Hameed","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2013,9,24]]},"reference":[{"issue":"1\u20132","key":"654_CR1","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1016\/j.mrfmmm.2006.06.010","volume":"601","author":"Y Hirai","year":"2006","unstructured":"Hirai Y, Kodama Y, Moriwaki S, Noda A, Cullings HM, Macphee DG, Kodama K, Mabuchi K, Kraemer KH, Land CE, Nakamura N: Heterozygous individuals bearing a founder mutation in the XPA DNA repair gene comprise nearly 1% of the Japanese population. 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