{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T17:08:55Z","timestamp":1788282535626,"version":"build-2803163510"},"reference-count":95,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,12,14]],"date-time":"2022-12-14T00:00:00Z","timestamp":1670976000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Mossakowski Medical Research Institute, Polish Academy of Sciences","award":["FBW016"],"award-info":[{"award-number":["FBW016"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Our aim was to analyze the phenotypic-genetic correlations in a patient diagnosed with early onset corticobasal syndrome with progressive non-fluent aphasia (CBS-PNFA), characterized by predominant apraxia of speech, accompanied by prominent right-sided upper-limb limb-kinetic apraxia, alien limb phenomenon, synkinesis, myoclonus, mild cortical sensory loss, and right-sided hemispatial neglect. Whole-exome sequencing (WES) identified rare single heterozygous variants in ATP7B (c.3207C&gt;A), SORL1 (c.352G&gt;A), SETX (c.2385_2387delAAA), and FOXP1 (c.1762G&gt;A) genes. The functional analysis revealed that the deletion in the SETX gene changed the splicing pattern, which was accompanied by lower SETX mRNA levels in the patient\u2019s fibroblasts, suggesting loss-of-function as the underlying mechanism. In addition, the patient\u2019s fibroblasts demonstrated altered mitochondrial architecture with decreased connectivity, compared to the control individuals. This is the first association of the CBS-PNFA phenotype with the most common ATP7B pathogenic variant p.H1069Q, previously linked to Wilson\u2019s disease, and early onset Parkinson\u2019s disease. This study expands the complex clinical spectrum related to variants in well-known disease genes, such as ATP7B, SORL1, SETX, and FOXP1, corroborating the hypothesis of oligogenic inheritance. To date, the FOXP1 gene has been linked exclusively to neurodevelopmental speech disorders, while our study highlights its possible relevance for adult-onset progressive apraxia of speech, which guarantees further study.<\/jats:p>","DOI":"10.3390\/genes13122361","type":"journal-article","created":{"date-parts":[[2022,12,15]],"date-time":"2022-12-15T02:20:57Z","timestamp":1671070857000},"page":"2361","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["A Patient with Corticobasal Syndrome and Progressive Non-Fluent Aphasia (CBS-PNFA), with Variants in ATP7B, SETX, SORL1, and FOXP1 Genes"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8670-1200","authenticated-orcid":false,"given":"Katarzyna","family":"Gaweda-Walerych","sequence":"first","affiliation":[{"name":"Department of Neurogenetics and Functional Genomics, Mossakowski Medical Research Institute, Polish Academy of Sciences, 02-106 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4141-072X","authenticated-orcid":false,"given":"Emilia J.","family":"Sitek","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Neuropsychology, Neurolinguistics and Neuropsychotherapy, Division of Neurological and Psychiatric Nursing, Faculty of Health Sciences, Medical University of Gdansk, 80-211 Gdansk, Poland"},{"name":"Neurology Department, St. Adalbert Hospital, Copernicus PL, 80-462 Gdansk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ma\u0142gorzata","family":"Borczyk","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmacogenomics, Department of Molecular Pharmacology, Maj Institute of Pharmacology Polish Academy of Sciences, 31-343 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ewa","family":"Naro\u017ca\u0144ska","sequence":"additional","affiliation":[{"name":"Neurology Department, St. Adalbert Hospital, Copernicus PL, 80-462 Gdansk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bogna","family":"Brockhuis","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Faculty of Health Sciences, Medical University of Gdansk, 80-214 Gdansk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4273-7401","authenticated-orcid":false,"given":"Micha\u0142","family":"Korosty\u0144ski","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmacogenomics, Department of Molecular Pharmacology, Maj Institute of Pharmacology Polish Academy of Sciences, 31-343 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3695-2612","authenticated-orcid":false,"given":"Micha\u0142","family":"Schinwelski","sequence":"additional","affiliation":[{"name":"Neurology Department, St. Adalbert Hospital, Copernicus PL, 80-462 Gdansk, Poland"},{"name":"Neurocentrum Miwomed, 80-207 Gdansk, Poland"},{"name":"Division of Neurological and Psychiatric Nursing, Faculty of Health Sciences, Medical University of Gdansk, 80-211 Gdansk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8219-2912","authenticated-orcid":false,"given":"Mariusz","family":"Siemi\u0144ski","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Faculty of Health Sciences, Medical University of Gdansk, 80-210 Gdansk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaros\u0142aw","family":"S\u0142awek","sequence":"additional","affiliation":[{"name":"Neurology Department, St. Adalbert Hospital, Copernicus PL, 80-462 Gdansk, Poland"},{"name":"Division of Neurological and Psychiatric Nursing, Faculty of Health Sciences, Medical University of Gdansk, 80-211 Gdansk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7332-8494","authenticated-orcid":false,"given":"Cezary","family":"Zekanowski","sequence":"additional","affiliation":[{"name":"Department of Neurogenetics and Functional Genomics, Mossakowski Medical Research Institute, Polish Academy of Sciences, 02-106 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1016\/j.jalz.2018.10.009","article-title":"Genetic screen in a large series of patients with primary progressive aphasia","volume":"15","author":"Ramos","year":"2019","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Arienti, F., Lazzeri, G., Vizziello, M., Monfrini, E., Bresolin, N., Saetti, M.C., Picillo, M., Franco, G., and Di Fonzo, A. 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