ArticleAmerican journal of human genetics2002
Alternative splicing in the alpha-galactosidase A gene: increased exon inclusion results in the Fabry cardiac phenotype.
Article in American journal of human genetics, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.
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Who cites it
77 citing papers in PubMed, 160 citations in OpenAlex.
- NovelJournal of clinical medicine · 2026Review
- Progressive conduction system disease preceding hypertrophy in IVS4+919G>A Fabry variant: a population-based electrocardiographic study.Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2026Article
- Beneficial bystander-enhanced cryptic splice rescue of cardiac-type Fabry GLA IVS4+919G>A by adenine base editing in patient fibroblasts.Gene therapy · 2026Article
- Newborn screening for Fabry disease in Japan: an additional 3-year report.Molecular genetics and metabolism reports · 2026Article
- Successful experience with high-risk and family screening for Fabry disease in Ninghai County, Zhejiang Province, Eastern China: genotype‒phenotype analysis of the GLA IVS4 + 919G > A variant.BMC medical genomics · 2026Article
- Two diseases presenting only as cardiac hypertrophy: differences between the late-onset Fabry disease cardiac variant and hypertrophic cardiomyopathy.BMC cardiovascular disorders · 2026Article
- A New Class of Pathogenic Non-Coding Variants in GLA.International journal of molecular sciences · 2026Article
- Rationale, Objectives and Study Design of the Taiwan Registry of Hypertrophic Cardiomyopathy (THIC).Acta Cardiologica Sinica · 2026Article
- Invention of an oral medication for cardiac Fabry disease caused by RNA mis-splicing.Science advances · 2025Article
- Heart failure in two male patients with late-onset Fabry mutation (IVS4 + 919G > A).ESC heart failure · 2025Article
- Long-read sequencing enables comprehensive molecular genetic diagnosis of Fabry disease.Human genomics · 2024Article
- Fabry Disease in Women: Genetic Basis, Available Biomarkers, and Clinical Manifestations.Genes · 2023Review
- All reported non-canonical splice site variants in GLA cause aberrant splicing.Clinical and experimental nephrology · 2023Article
- Population Frequency of Undiagnosed Fabry Disease in the General Population.Kidney international reports · 2023Article
- Newborn Screening for Fabry Disease: Current Status of Knowledge.International journal of neonatal screening · 2023Review
- Functional characterization of human genomic variation linked to polygenic diseases.Trends in genetics : TIG · 2023Review
- Advanced searching for hypertrophic cardiomyopathy heritability in real practice tomorrow.Frontiers in cardiovascular medicine · 2023Review
- Abnormal Pre-mRNA Splicing in Exonic Fabry Disease-Causing GLA Mutations.International journal of molecular sciences · 2022Article
- An Overview of Molecular Mechanisms in Fabry Disease.Biomolecules · 2022Review
- Identification and functional characterization of the first deep intronic GLA mutation (IVS4+1326C>T) causing renal variant of Fabry disease.Orphanet journal of rare diseases · 2022Article
17 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Fabry disease is an inborn error of glycosphingolipid catabolism, resulting from deficient activity of lysosomal alpha-galactosidase A (alpha-Gal A). A rare alternative splicing that introduces a 57-nucleotide (nt) intronic sequence to the alpha-Gal A transcript from intron 4 of the gene has been identified. In addition, a novel midintronic base substitution that results in substantially increased alternative splicing has been identified in a patient with Fabry disease who has the cardiac variant phenotype. The sequence of the patient's intron 4 contains a single G-->A transversion at genomic nt 9331 (IVS4+919 G-->A ), located at the minus sign4 position of the 3' end of the intronic insertion (nts 9278--9334 in the genomic sequence). Minigene constructs containing the entire intron 4 sequence with G, A, C, or T at nt 9331 within an alpha-Gal A complementary DNA expression vector were prepared and expressed in COS-1 cells. Whereas transfection of the G or T minigenes transcribed predominantly normal-sized transcripts, the transfection of the A or C minigenes produced a large amount of the alternatively spliced transcript. These results suggest that the G-->A mutation, within an A/C-rich domain, results in increased recognition of the alternative splicing by an A/C-rich enhancer-type exonic splicing enhancer. The intronic mutation was not observed in 100 unrelated unaffected men but was present in 6 unrelated patients with cardiac Fabry disease. Reverse-transcriptase polymerase chain reaction of total RNA of various normal human tissues revealed that the alternatively spliced transcript was present in all of the samples, and especially at a higher ratio in the lung and muscle. The normal transcript was present in the patients' lymphoblasts and resulted in approximately 10% residual enzyme activity, leading to a cardiac phenotype of Fabry disease.
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