Related Experiment Video
Updated: Dec 25, 2025
In Vitro Enzyme Measurement to Test Pharmacological Chaperone Responsiveness in Fabry and Pompe Disease
Published on: December 20, 2017
The Fabry disease-causing mutation, GLA IVS4+919G>A, originated in Mainland China more than 800 years ago
Kung-Hao Liang1,2,3, Yung-Hsiu Lu4, Chih-Wei Niu4
1Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan.
Insights
The GLA IVS4+919G>A mutation, linked to Fabry disease, originated in a Chinese chromosome over 800 years ago. This finding stems from analyzing a shared haplotype among affected individuals across Asia.
Area of Science:
- Genetics
- Population Genetics
- Medical Genetics
Background:
- The GLA IVS4+919G>A mutation is a prevalent cause of Fabry disease, particularly noted in Taiwanese patients with hypertrophic cardiomyopathy.
- This X-linked mutation has been identified in diverse Asian populations, including Japan, Southeast Asia, and China.
Purpose of the Study:
- To determine the ancestral origin and age of the GLA IVS4+919G>A mutation.
- To investigate the mutation's prevalence and founder effect across various Asian populations.
Main Methods:
- Dense genotyping using the Illumina Infinium CoreExome-24 microarray was performed on 33 male patients carrying the GLA IVS4+919G>A mutation.
- Haplotype analysis was conducted to identify shared genetic markers among patients and compare them with healthy individuals.
- Linkage-disequilibrium decay theory was applied to estimate the mutation's age based on haplotype lengths.
Main Results:
- A distinct mutation-carrying haplotype was identified in all 33 studied patients, absent in healthy controls.
- Significant haplotype diversity around the mutation site supports a single founder event.
- Age estimation indicated the mutation originated more than 800 years ago, with a median estimate of 922.6 years.
Conclusions:
- The GLA IVS4+919G>A mutation arose from a single ancestral event in a Chinese chromosome over eight centuries ago.
- The study confirms a founder effect for this Fabry disease mutation in Asian populations.
- Understanding the mutation's origin aids in genetic counseling and understanding disease prevalence.
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.
More Related Videos
03:45Investigating the Pathogenesis of MYH7 Mutation Gly823Glu in Familial Hypertrophic Cardiomyopathy using a Mouse Model
Published on: August 8, 2022
08:22A Robust Polymerase Chain Reaction-based Assay for Quantifying Cytosine-guanine-guanine Trinucleotide Repeats in Fragile X Mental Retardation-1 Gene
Published on: September 16, 2019
Related Concept Videos
02:32Exon Recombination
Exon shuffling follows “splice frame rules.” Each exon...
02:59Animal Mitochondrial Genetics
01:31Translation
Translation Produces the Building Blocks of Life
Proteins are...
01:31Translation
Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
Translation Produces the Building Blocks of...
01:23Cystic Fibrosis: Pathogenesis
CF is primarily caused by a genetic mutation in a chromosome 7 gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common gene mutation leading to CF is the ΔF508 mutation,...
02:37Gene Duplication and Divergence
The duplicated copies of the gene are called Paralogs. Paralogs with similar sequences and functions form a gene family. Across several species, a large number of gene families are...