{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,24]],"date-time":"2025-05-24T04:29:51Z","timestamp":1748060991740,"version":"3.37.3"},"reference-count":20,"publisher":"Springer Science and Business Media LLC","issue":"11","license":[{"start":{"date-parts":[[2022,7,20]],"date-time":"2022-07-20T00:00:00Z","timestamp":1658275200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,7,20]],"date-time":"2022-07-20T00:00:00Z","timestamp":1658275200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100007065","name":"Universit\u00e0 degli Studi di Salerno","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100007065","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Neurol"],"published-print":{"date-parts":[[2022,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Introduction<\/jats:title>\n                <jats:p>Progranulin (<jats:italic>PGRN<\/jats:italic>) is a secreted glycoprotein encoded in humans by the <jats:italic>GRN<\/jats:italic> gene, located on chromosome 17q21. Several nonsense and missense pathogenetic <jats:italic>GRN<\/jats:italic> mutations have been described.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Objective<\/jats:title>\n                <jats:p>We herein describe two sisters carrying a rare <jats:italic>GRN<\/jats:italic> mutation with extremely different clinical features and family history of dementia and behavioral disorders, with a novel presentation with stridor and dysphonia.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Patients underwent a multidimensional assessment including neurological and neuropsychological evaluation, structural and functional imaging, and genetic screening.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>The younger sister presented at the age of 64 with inspiratory stridor, dysphonia and exercise-induced dyspnea. Transnasal fiberoptic laryngoscopy showed bilateral adduction of the vocal cords at rest and paradoxical further adduction of the vocal cords during forced inspiration, suggesting the hypothesis of an adductor laryngeal dystonia. The older sister presented at the age of 63 with a rapidly progressive corticobasal syndrome. The only clinical feature common to both sisters was a dysexecutive syndrome. The c.893G\u2009&gt;\u2009A mutation in exon 9 of <jats:italic>GRN<\/jats:italic> was found in heterozygosis in both sisters, causing a missense Arginine to Histidine substitution in position 298 of the protein (p.R298H).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Our report supports the pathogenicity of the <jats:italic>GRN<\/jats:italic> p.R298H mutation, which is first detected in two members from the same family, showing an extremely different phenotypes. Moreover, we report the first case of an FTD-associated mutation presenting with inspiratory stridor and dysphonia linked to adductor laryngeal dystonia, thus expanding the clinical spectrum of GRN-related disorders.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00415-022-11285-7","type":"journal-article","created":{"date-parts":[[2022,7,20]],"date-time":"2022-07-20T22:02:27Z","timestamp":1658354547000},"page":"6170-6177","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A novel phenotype in an Italian family with a rare progranulin mutation"],"prefix":"10.1007","volume":"269","author":[{"given":"Maria Claudia","family":"Russillo","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristiano","family":"Sorrentino","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alfonso","family":"Scarpa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia","family":"Vinciguerra","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giulio","family":"Cicarelli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sofia","family":"Cuoco","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monica","family":"Gagliardi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariagrazia","family":"Talarico","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Radha","family":"Procopio","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Quattrone","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paolo","family":"Barone","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6217-313X","authenticated-orcid":false,"given":"Maria Teresa","family":"Pellecchia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,7,20]]},"reference":[{"issue":"11","key":"11285_CR1","doi-asserted-by":"publisher","first-page":"1245","DOI":"10.1002\/bies.200900086","volume":"31","author":"A Bateman","year":"2009","unstructured":"Bateman A, Bennett HP (2009) The granulin gene family: from cancer to dementia. 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