{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:22:17Z","timestamp":1791246137124,"version":"4.1.0"},"reference-count":32,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2011,4,28]],"date-time":"2011-04-28T00:00:00Z","timestamp":1303948800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2011,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Optic atrophy (OA) and sensorineural hearing loss (SNHL) are key abnormalities in several syndromes, including the recessively inherited Wolfram syndrome, caused by mutations in\n                    <jats:italic>WFS1<\/jats:italic>\n                    . In contrast, the association of autosomal dominant OA and SNHL without other phenotypic abnormalities is rare, and almost exclusively attributed to mutations in the Optic Atrophy\u20101 gene (\n                    <jats:italic>OPA1<\/jats:italic>\n                    ), most commonly the p.R445H mutation. We present eight probands and their families from the US, Sweden, and UK with OA and SNHL, whom we analyzed for mutations in\n                    <jats:italic>OPA1<\/jats:italic>\n                    and\n                    <jats:italic>WFS1<\/jats:italic>\n                    . Among these families, we found three heterozygous missense mutations in\n                    <jats:italic>WFS1<\/jats:italic>\n                    segregating with OA and SNHL: p.A684V (six families), and two novel mutations, p.G780S and p.D797Y, all involving evolutionarily conserved amino acids and absent from 298 control chromosomes. Importantly, none of these families harbored the\n                    <jats:italic>OPA1<\/jats:italic>\n                    p.R445H mutation. No mitochondrial DNA deletions were detected in muscle from one p.A684V patient analyzed. Finally, wolframin p.A684V mutant ectopically expressed in HEK cells showed reduced protein levels compared to wild\u2010type wolframin, strongly indicating that the mutation is disease\u2010causing. Our data support OA and SNHL as a phenotype caused by dominant mutations in\n                    <jats:italic>WFS1<\/jats:italic>\n                    in these additional eight families. Importantly, our data provide the first evidence that a single, recurrent mutation in\n                    <jats:italic>WFS1<\/jats:italic>\n                    , p.A684V, may be a common cause of ADOA and SNHL, similar to the role played by the p.R445H mutation in\n                    <jats:italic>OPA1<\/jats:italic>\n                    . Our findings suggest that patients who are heterozygous for\n                    <jats:italic>WFS1<\/jats:italic>\n                    missense mutations should be carefully clinically examined for OA and other manifestations of Wolfram syndrome. \u00a9 2011 Wiley\u2010Liss, Inc.\n                  <\/jats:p>","DOI":"10.1002\/ajmg.a.33970","type":"journal-article","created":{"date-parts":[[2011,4,28]],"date-time":"2011-04-28T13:32:32Z","timestamp":1303997552000},"page":"1298-1313","source":"Crossref","is-referenced-by-count":116,"title":["Identification of p.A684V missense mutation in the\n                    <i>WFS1<\/i>\n                    gene as a frequent cause of autosomal dominant optic atrophy and hearing impairment"],"prefix":"10.1002","volume":"155","author":[{"given":"Nanna D.","family":"Rendtorff","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianne","family":"Lodahl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Houda","family":"Boulahbel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ida R.","family":"Johansen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arti","family":"Pandya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine O.","family":"Welch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virginia W.","family":"Norris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen 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