P.E66Q mutation in the GLA gene is associated with a high risk of cerebral small‐vessel occlusion in elderly Japanese males. (31st May 2013)

• Record Type: Journal Article
• Authors: Nakamura, K.; Sekijima, Y.; Nakamura, K.; Hattori, K.; Nagamatsu, K.; Shimizu, Y.; Yazaki, M.; Sakurai, A.; Endo, F.; Fukushima, Y.; Ikeda, S.‐I.
• Is Part Of: European journal of neurology. Volume 21:Number 1(2014:Jan.)
• Page Start: 49
• Page End: 56
• Publication Date: 2013-05-31
• Subjects: Neurology -- Periodicals; Nervous system -- Diseases -- Periodicals; 616.8
• DOI: 10.1111/ene.12214
• Languages: English
• ISSNs: 1351-5101

Abstract

<abstract abstract-type="main" id="ene12214-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="ene12214-sec-0001" sec-type="section"> <title>Background and purpose</title> <p> <italic>GLA</italic> is the causative gene of Fabry disease, an X‐linked lysosomal storage disorder resulting from α‐galactosidase A (α‐GAL) deficiency. Stroke is an important manifestation of Fabry disease, and recent epidemiological studies have indicated that up to 4.9% of young male cryptogenic stroke patients have <italic>GLA</italic> mutations. To determine the importance of <italic>GLA</italic> mutations in the general stroke population, the frequency of <italic>GLA</italic> mutations in Japanese male ischaemic stroke (IS) patients with various risk factors and ages was measured.</p> </sec> <sec id="ene12214-sec-0002" sec-type="section"> <title>Methods</title> <p>A total of 475 male IS patients (mean age 69.7 ± 12.5 years), were enrolled in this study. A blood sample was obtained to produce blood spots for measurement of α‐GAL activity. Blood samples with decreased enzymatic activity were reassayed and the entire <italic>GLA</italic> gene was analyzed by direct DNA sequencing if α‐Gal A activity was consistently low.</p> </sec> <sec id="ene12214-sec-0003" sec-type="section"> <title>Results</title> <p>α‐Gal A activity was decreased in 10 men, five of whom (1.1%) had the <italic>GLA</italic> gene mutation, p.E66Q. All IS patients with p.E66Q mutation had substantial residual α‐Gal A activity, in contrast to patients with classic‐type Fabry disease. Clinically, all patients with p.E66Q mutation were > 50 years old and had multiple small‐vessel occlusions (lacunar infarctions). Statistical analysis using Fisher's exact test showed the allele frequency of <italic>GLA</italic> p.E66Q in patients with small‐vessel occlusion to be significantly higher than that in the general Japanese population [odds ratio (OR) = 3.34, <italic>P </italic>=<italic> </italic>0.025).</p> </sec> <sec id="ene12214-sec-0004" sec-type="section"> <title>Conclusions</title> <p> <italic>GLA</italic> p.E66Q mutation is a genetic risk factor for cerebral small‐vessel occlusion in elderly Japanese males.</p> </sec> </abstract>