1. The Fabry disease-causing mutation, GLA IVS4+919G>A, originated in Mainland China more than 800 years ago.
- Author
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Liang KH, Lu YH, Niu CW, Chang SK, Chen YR, Cheng CY, Hsu TR, Yang CF, Nakamura K, and Niu DM
- Subjects
- Adult, Cardiomyopathy, Hypertrophic, Familial epidemiology, Cardiomyopathy, Hypertrophic, Familial pathology, China epidemiology, Fabry Disease epidemiology, Fabry Disease pathology, Genes, X-Linked genetics, Genotype, Haplotypes genetics, Humans, Japan epidemiology, Malaysia epidemiology, Male, Middle Aged, Mutation genetics, Taiwan epidemiology, Cardiomyopathy, Hypertrophic, Familial genetics, Fabry Disease genetics, alpha-Galactosidase genetics
- Abstract
The Fabry disease-causing mutation, the GLA IVS4+919G>A (designated GLA IVS4), is very prevalent in patients with hypertrophic cardiomyopathy in Taiwan. This X-linked mutation has also been found in patients in Kyushu, Japan and Southeast Asia. To investigate the age and the possible ancestral origin of this mutation, a total of 33 male patients with the GLA IVS4+919G>A mutation, born in Taiwan, Japan, Singapore, Malaysia, Vietnam, and the Fujian and Guangdong provinces of China, were studied. Peripheral bloods were collected, and the Ilumina Infinium CoreExome-24 microarray was used for dense genotyping. A mutation-carrying haplotype was discovered which was shared by all 33 patients. This haplotype does not exist in 15 healthy persons without the mutation. Rather, a wide diversity of haplotypes was found in the vicinity of the mutation site, supporting the existence of a single founder of the GLA IVS4 mutation. The age of the founder mutation was estimated by the lengths of the mutation-carrying haplotypes based on the linkage-disequilibrium decay theory. The first, second, and third quartile of the age estimates are 800.7, 922.6, and 1068.4 years, respectively. We concluded that the GLA IVS4+919G>A mutation originated from a single mutational event that occurred in a Chinese chromosome more than 800 years ago.
- Published
- 2020
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