{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T06:07:51Z","timestamp":1761718071560},"reference-count":38,"publisher":"Wiley","issue":"S2","license":[{"start":{"date-parts":[[2008,11,3]],"date-time":"2008-11-03T00:00:00Z","timestamp":1225670400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100004329","name":"Genzyme","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004329","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2008,12]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Subnormal leukocyte \u03b1\u2010galactosidase (\u03b1\u2010Gal) activity was found during evaluation of an adolescent male with cryptogenic cerebrovascular small\u2010vessel disease. The only molecular abnormality found was the g.1170C&gt;T single\u2010nucleotide polymorphism (SNP) in the 5\u2032 untranslated region of exon 1 in the \u03b1\u2010Gal gene (<jats:italic>GLA<\/jats:italic>). Historically, this polymorphism has been considered to be biologically neutral. To test the hypothesis that the g.1170T allele might be associated with lower \u03b1\u2010Gal expression, we genotyped <jats:italic>GLA<\/jats:italic> exon 1 and measured leukocyte and plasma \u03b1\u2010Gal in the parents, brother and sister of the index case. The g.1170T allele co\u2010segregated with a subnormal leukocyte \u03b1\u2010Gal activity in the three siblings. Although plasma enzyme activities were within the normal range in all five relatives, the ranking of their values suggested a dosage effect of the g.1170T allele. Western blotting assays of leukocyte protein extracts showed that the relative expression of \u03b1\u2010Gal in both the patient and his sister was significantly lower than in sex\u2010matched hemizygous or homozygous controls for the g.1170C allele, either normalized to the \u03b2\u2010actin immunoblot expression or standardized to a known amount of recombinant human \u03b1\u2010Gal. These family data, in combination with results from a recent <jats:italic>GLA<\/jats:italic> SNP screening study among healthy Portuguese individuals, suggest that the g.1170C&gt;T SNP may be co\u2010dominantly associated with a relatively decreased <jats:italic>GLA<\/jats:italic> expression at the transcription and\/or translation level. Larger population studies are needed to confirm these findings and to test the hypothesis that the <jats:italic>GLA<\/jats:italic> g.1170C&gt;T may contribute to the multifactorial risk of ischaemic small\u2010vessel cerebrovascular disease.<\/jats:p>","DOI":"10.1007\/s10545-008-0972-0","type":"journal-article","created":{"date-parts":[[2008,10,31]],"date-time":"2008-10-31T17:40:04Z","timestamp":1225474804000},"page":"405-413","source":"Crossref","is-referenced-by-count":18,"title":["The g.1170C&gt;T polymorphism of the 5\u2032 untranslated region of the human alpha\u2010galactosidase gene is associated with decreased enzyme expression\u2014Evidence from a family study"],"prefix":"10.1002","volume":"31","author":[{"given":"J. P.","family":"Oliveira","sequence":"first","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medicine University of Porto Alameda Hern\u00e2ni Monteiro Porto 4200\u2010319 Portugal"},{"name":"Department of Clinical Genetics Hospital S\u00e3o Jo\u00e3o Porto Portugal"}]},{"given":"S.","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medicine University of Porto Alameda Hern\u00e2ni Monteiro Porto 4200\u2010319 Portugal"}]},{"given":"C.","family":"Reguenga","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular and Molecular Biology, Faculty of Medicine University of Porto Porto Portugal"}]},{"given":"F.","family":"Carvalho","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medicine University of Porto Alameda Hern\u00e2ni Monteiro Porto 4200\u2010319 Portugal"}]},{"given":"J.\u2010E.","family":"M\u00e5nsson","sequence":"additional","affiliation":[{"name":"Neurochemistry Laboratory Sahlgren's University Hospital Molndal Sweden"}]}],"member":"311","published-online":{"date-parts":[[2008,11,3]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.2310\/6650.2002.33432"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.85.11.3903"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM197307052890103"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.30.8.658"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.76.10.5326"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1006\/rwgn.2001.0443"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1159\/000060184"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000173030.70057.eb"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1005366224351"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V84.7.2376.2376"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V83.10.2899.2899"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.10423"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2006080816"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/123.9.1784"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)68230-4"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/17.8.3301"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)54860-2"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.3109\/00365519609088605"},{"key":"e_1_2_6_20_1","first-page":"18.30","volume-title":"Molecular 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