{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T03:47:21Z","timestamp":1775447241016,"version":"3.50.1"},"reference-count":13,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,2,2]],"date-time":"2023-02-02T00:00:00Z","timestamp":1675296000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p>Variants in the <jats:italic>ERCC4<\/jats:italic> gene have been described to be associated with the following autosomal recessive diseases: xeroderma pigmentosum group F (XPF), xeroderma pigmentosum type F\/Cockayne syndrome (XPF\/CS), Fanconi anemia complementation group Q (FANCQ), and XFE progeroid syndrome (XFEPS). In this paper, we present a case of a 53-year-old Caucasian female patient with rare variants in the <jats:italic>ERCC4<\/jats:italic> gene. When she was 42\u00a0years old, falls and loss of balance occurred. At the age of 48, involuntary, uncoordinated movements of the upper limbs and head, tongue stereotypes (licking and extending movements), speech problems (dysarthria), memory deterioration, and hearing loss occurred. Since childhood, she has shown hypersensitivity to UV radiation. The neurological examination revealed chorea syndrome, cerebellar ataxia, dysarthria, and bilateral hearing loss. She has numerous pigmented lesions on the skin. Brain MRI demonstrated massive cortico-subcortical atrophy. The neuropsychological examination revealed dysfunctions in the executive domain in terms of attention, working memory, organizing, and planning activities. The genetic diagnostics was performed which excluded spinocerebellar ataxia types 1, 2, 3, 6, and 17, Huntington\u2019s disease, and FMR1 premutation. In the genetic analysis of next-generation sequencing (NGS), two variants: c.2395C &amp;gt; T and c.1349G &amp;gt; A in the <jats:italic>ERCC4<\/jats:italic> gene were identified in a heterozygote configuration. So far, a few cases of <jats:italic>ERCC4<\/jats:italic> gene variants, which are associated with nucleotide excision repair pathways, have been described in connection with symptoms of cerebellar ataxia. In patients with ERCC4 biallelic variants, the adult neurological phenotype can sometimes be the first symptom and reason for access to genetic testing. The aforementioned case highlights the occurrence of rare genetic causes of progressive neurodegenerative diseases in adults, especially with the spectrum of autosomal recessive nucleotide excision repair pathway disorders (NERDs).<\/jats:p>","DOI":"10.3389\/fgene.2023.1107460","type":"journal-article","created":{"date-parts":[[2023,2,2]],"date-time":"2023-02-02T06:48:06Z","timestamp":1675320486000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Case report: Variants in the ERCC4 gene as a rare cause of cerebellar ataxia with chorea"],"prefix":"10.3389","volume":"14","author":[{"given":"Joanna","family":"Kulikowska","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Jakubiuk-Tomaszuk","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ma\u0142gorzata","family":"Rydzanicz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rafa\u0142","family":"P\u0142oski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan","family":"Kochanowicz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alina","family":"Kulakowska","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katarzyna","family":"Kapica-Topczewska","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2023,2,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"800","DOI":"10.1016\/J.AJHG.2013.04.002","article-title":"Mutations in ERCC4, encoding the DNA-repair endonuclease XPF, cause Fanconi anemia","volume":"92","author":"Bogliolo","year":"2013","journal-title":"Am. J. Hum. Genet."},{"key":"B2","doi-asserted-by":"publisher","first-page":"800","DOI":"10.1016\/J.AJHG.2013.04.002","article-title":"Mutations in ERCC4, encoding the DNA-repair endonuclease XPF, cause Fanconi anemia","volume":"92","author":"Bogliolo","year":"2013","journal-title":"Am. J. Hum. Genet."},{"key":"B3","doi-asserted-by":"publisher","first-page":"342","DOI":"10.1159\/000526237","article-title":"Chorea: An update on genetics","volume":"85","author":"Burgunder","year":"2022","journal-title":"Eur. Neurol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"1707","DOI":"10.1002\/MDS.29071","article-title":"Adult-onset neurodegeneration in nucleotide excision repair disorders (NERDND): Time to move beyond the skin","volume":"37","author":"Cordts","year":"2022","journal-title":"Mov. Disord."},{"key":"B5","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1038\/S10038-017-0408-5","article-title":"Cerebellar ataxia-dominant phenotype in patients with ERCC4 mutations","volume":"63","author":"Doi","year":"2018","journal-title":"J. Hum. Genet."},{"key":"B6","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1111\/CGE.13611","article-title":"Syndromic chorioretinal coloboma associated with heterozygous de novo RARA mutation affecting an amino acid critical for retinoic acid interaction","volume":"96","author":"Jakubiuk-Tomaszuk","year":"2019","journal-title":"Clin. Genet."},{"key":"B7","doi-asserted-by":"publisher","first-page":"807","DOI":"10.1016\/J.AJHG.2013.04.007","article-title":"Malfunction of nuclease ERCC1-XPF results in diverse clinical manifestations and causes Cockayne syndrome, xeroderma pigmentosum, and Fanconi anemia","volume":"92","author":"Kashiyama","year":"2013","journal-title":"Am. J. Hum. Genet."},{"key":"B8","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1002\/HUMU.23367","article-title":"ERCC4 variants identified in a cohort of patients with segmental progeroid syndromes","volume":"39","author":"Mori","year":"2018","journal-title":"Hum. Mutat."},{"key":"B9","doi-asserted-by":"publisher","first-page":"650639","DOI":"10.3389\/FGENE.2021.650639","article-title":"Case report: Identification of novel variants in ERCC4 and DDB2 genes in two Tunisian patients with atypical xeroderma pigmentosum phenotype","volume":"12","author":"Nabouli","year":"2021","journal-title":"Front. Genet."},{"key":"B10","doi-asserted-by":"publisher","first-page":"e240","DOI":"10.1212\/NXG.0000000000000240","article-title":"Neurodegeneration as the presenting symptom in 2 adults with xeroderma pigmentosum complementation group F","volume":"4","author":"Shanbhag","year":"2018","journal-title":"Neurol. Genet."},{"key":"B11","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/J.DNAREP.2015.09.003","article-title":"Nucleotide excision repair in humans","volume":"36","author":"Spivak","year":"2015","journal-title":"DNA Repair (Amst)"},{"key":"B12","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1007\/S12185-020-03010-9","article-title":"Characterization of hereditary red blood cell membranopathies using combined targeted next-generation sequencing and osmotic gradient ektacytometry","volume":"113","author":"Vives-Corrons","year":"2021","journal-title":"Int. J. Hematol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"652376","DOI":"10.3389\/FGENE.2021.652376","article-title":"Preliminary study on the clinical and genetic characteristics of hereditary spherocytosis in 15 Chinese children","volume":"12","author":"Wu","year":"2021","journal-title":"Front. Genet."}],"container-title":["Frontiers in Genetics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2023.1107460\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,2]],"date-time":"2023-02-02T06:48:07Z","timestamp":1675320487000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2023.1107460\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,2]]},"references-count":13,"alternative-id":["10.3389\/fgene.2023.1107460"],"URL":"https:\/\/doi.org\/10.3389\/fgene.2023.1107460","relation":{},"ISSN":["1664-8021"],"issn-type":[{"value":"1664-8021","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,2]]},"article-number":"1107460"}}