{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T09:08:50Z","timestamp":1769764130504,"version":"3.49.0"},"reference-count":22,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,8,16]],"date-time":"2021-08-16T00:00:00Z","timestamp":1629072000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009574","name":"Servicio Murciano de Salud","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009574","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p>We aimed to determine if an adolescent patient presenting with neurological impairment has xeroderma pigmentosum (XP). For this purpose, whole-exome sequencing was performed to assess mutations in <jats:italic>XP<\/jats:italic> genes. Dermal fibroblasts were established from a skin biopsy and XPA expression determined by immunoblotting. Nucleotide excision repair (NER) capacity was measured by detection of unscheduled DNA synthesis (UDS) in UVC-irradiated patient fibroblasts. Genetic analysis revealed two recessive mutations in <jats:italic>XPA<\/jats:italic>, one known c.682C&amp;gt;T, p.Arg228Ter, and the other c.553C&amp;gt;T, p.Gln185Ter, only two cases were reported. XPA protein was virtually undetectable in lysates from patient-derived fibroblast. The patient had significantly lower UV-induced UDS (3.03 \u00b1 1.95%, <jats:italic>p<\/jats:italic> &amp;lt; 0.0001) compared with healthy controls (C5RO = 100 \u00b1 12.2; C1UMN = 118 \u00b1 5.87), indicating significant NER impairment. In conclusion, measurement of NER capacity is beneficial for the diagnosis of XP and in understanding the functional impact of novel mutations in <jats:italic>XP<\/jats:italic> genes. Our findings highlight the importance of neurologists considering XP in their differential diagnosis when evaluating patients with atypical neurodegeneration.<\/jats:p>","DOI":"10.3389\/fgene.2021.717361","type":"journal-article","created":{"date-parts":[[2021,8,16]],"date-time":"2021-08-16T07:06:17Z","timestamp":1629097577000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Case Report: Identification of a Heterozygous XPA c.553C&gt;T Mutation Causing Neurological Impairment in a Case of Xeroderma Pigmentosum Complementation Group A"],"prefix":"10.3389","volume":"12","author":[{"given":"Juan Antonio","family":"Garc\u00eda-Carmona","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew J.","family":"Yousefzadeh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fernando","family":"Alarc\u00f3n-Soldevilla","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eva","family":"Fages-Caravaca","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tra L.","family":"Kieu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariah A.","family":"Witt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"\u00c1ngel","family":"L\u00f3pez-\u00c1vila","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura J.","family":"Niedernhofer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9 Antonio","family":"P\u00e9rez-Vicente","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,8,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1016\/j.gene.2013.09.125","article-title":"Mutational spectrum of Xeroderma pigmentosum group A in Egyptian patients","volume":"533","author":"Amr","year":"2014","journal-title":"Gene"},{"key":"B2","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1016\/0921-8777(94)90034-5","article-title":"The XPA protein is a zinc metalloprotein with an ability to recognize various kinds of DNA damage","volume":"315","author":"Asahina","year":"1994","journal-title":"Mutat. 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