{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T10:53:09Z","timestamp":1790679189777,"version":"4.1.0"},"reference-count":42,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2011,5,25]],"date-time":"2011-05-25T00:00:00Z","timestamp":1306281600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2012,3]]},"abstract":"<jats:p>Ferri L, Guido C, la Marca G, Malvagia S, Cavicchi C, Fiumara A, Barone R, Parini R, Antuzzi D, Feliciani C, Zampetti A, Manna R, Giglio S, Della Valle CM, Wu X, Valenzano KJ, Benjamin ER, Donati MA, Guerrini R, Genuardi M, Morrone A. Fabry disease: polymorphic haplotypes and a novel missense mutation in the <jats:italic>GLA<\/jats:italic> gene.<\/jats:p><jats:p>Fabry disease (FD) is an X\u2010linked lysosomal storage disorder with a heterogeneous spectrum of clinical manifestations that are caused by the deficiency of <jats:italic>\u03b1<\/jats:italic>\u2010galactosidase A (<jats:italic>\u03b1<\/jats:italic>\u2010Gal\u2010A) activity. Although useful for diagnosis in males, enzyme activity is not a reliable biochemical marker in heterozygous females due to random X\u2010chromosome inactivation, thus rendering DNA sequencing of the <jats:italic>\u03b1<\/jats:italic>\u2010Gal\u2010A gene, alpha\u2010galactosidase gene (<jats:italic>GLA<\/jats:italic>), the most reliable test for the confirmation of diagnosis in females. The spectrum of <jats:italic>GLA<\/jats:italic> mutations is highly heterogeneous. Many polymorphic <jats:italic>GLA<\/jats:italic> variants have been described, but it is unclear if haplotypes formed by combinations of such variants correlate with FD, thus complicating molecular diagnosis in females with normal <jats:italic>\u03b1<\/jats:italic>\u2010Gal\u2010A activity. We tested 67 female probands with clinical manifestations that may be associated with FD and 110 control males with normal <jats:italic>\u03b1<\/jats:italic>\u2010Gal\u2010A activity. Five different combinations of <jats:italic>GLA<\/jats:italic> polymorphic variants were identified in 14 of the 67 females, whereas clearcut pathogenetic alterations, p.Met51Ile and p.Met290Leu, were identified in two cases. The latter has not been reported so far, and both mutant forms were found to be responsive to the pharmacological chaperone deoxygalactonojirimycin (DGJ; migalastat hydrochloride). Analysis of the male control population, as well as male relatives of a suspected FD female proband, permitted the identification of seven different <jats:italic>GLA<\/jats:italic> gene haplotypes in strong linkage disequilibrium. The identification of haplotypes in control males provides evidence against their involvement in the development of FD phenotypic manifestations.<\/jats:p>","DOI":"10.1111\/j.1399-0004.2011.01689.x","type":"journal-article","created":{"date-parts":[[2011,4,25]],"date-time":"2011-04-25T16:22:17Z","timestamp":1303748537000},"page":"224-233","source":"Crossref","is-referenced-by-count":29,"title":["Fabry disease: polymorphic haplotypes and a novel missense mutation in the <i>GLA<\/i> gene"],"prefix":"10.1111","volume":"81","author":[{"given":"L","family":"Ferri","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"Guido","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G","family":"la 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