1998 Fiscal Year Final Research Report Summary
Study of gene mutations of cardiac Fabry disease
| Project/Area Number |
09470173
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Kagoshima University |
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Principal Investigator |
NAKAO Shoichiro Faculty of Medicine, Kagoshima University, Associate Professor, 医学部, 助教授 (90155664)
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| Co-Investigator(Kenkyū-buntansha) |
BIRO Sadatoshi University Hospital, Kagoshima University, Assistant Professor, 医学部・附属病院, 講師 (50244231)
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| Project Period (FY) |
1997 – 1998
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| Keywords | Cardiac Fabry disease / alpha-galactosidase / left venricular hypertrophy |
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| Research Abstract |
Fabry disease is an X-linked recessive disorder that results from deficiency of alpha-galactosidase (alpha-Gal). We have reported that cardiac Fabry disease had clinical manifestations limited to the heart and the incidence is about 3% among male patients with left ventricular hypertrophy (LVH). However, cardiac findings and enzyme activity have not been studied in male patients (hemizygotes) and female patients (heterozygotes) in cardiac Fabry families.
Methods : To clarify gene mutations, a-Gal activity and cardiac findings, we performed DNA analysis, and measured plasam alpha-Gal activity, and assessed LVH (13mm or greater) by echocardiography in seven cardiac Fabry families. Results : Three point mutations were detected in three of the seven families. These mutations were Ala20Pro in exon 1, Glu66G1n in exon 2, and Met296I1e in exon 6. Remaining four families did not have any mutations in the coding region of the alpha-Gal gene, but markedly decreased amount of a-Gal messenger RNA by Northern blot analysis. Eleven hemizygotes (in age 12 - 72 years) and fifteen heterozygotes (in age 27 - 84 years) were diagnosed in seven cardiac Fabry families by DNA analysis or measurements of alpha-Gal activity. All hemizygotes had very low activitiy of alpha-Gal. Twelve of the 15 heterozygotes had moderately low activities, but remaining three had normal activities. These three heterozygotes with a mutation of Glu66Gln in exon 2, needed DNA analysis to make diagnosis. All hemizygotes had LVH except one, who was 12-year-old. Three of the 10 hemizygotes had asymmetrical septal hypertrophy. None had left ventricular outflow obstruction. All fifteen heterozygotes did not have LVH.Conclusions : DNA analysis was useful to detect heterozygotes, because some hetrozygotes had normal alpha-Gal activity. LVH was observed in almost all hemizygotes but not in all heterozygotes in the cardiac Fabry families. Cardiac Fabry disease shows an X-linked left ventricular hypertrophy.
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