Newborn screening for Fabry disease in Taiwan reveals a high incidence of the later-onsetGLAmutation c.936+919G>A (IVS4+919G>A)
| Autor: | May-Chin Chao, Shu-Chuan Chiang, Robert J. Desnick, Hui-Ying Yeh, Shio Jean Lin, Wuh-Liang Hwu, Robert Dobrovolny, Yin-Hsiu Chien, Ai-Chu Huang, Li-Wen Hsu, Ni-Chung Lee, Teruo Kitagawa |
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| Rok vydání: | 2009 |
| Předmět: |
Male
medicine.medical_specialty Molecular Sequence Data Taiwan Disease Biology medicine.disease_cause Gastroenterology Article Neonatal Screening Internal medicine Genetics medicine Humans splice Amino Acid Sequence Age of Onset Genetics (clinical) Mutation Newborn screening Sequence Homology Amino Acid Incidence Incidence (epidemiology) Infant Newborn Heterozygote advantage medicine.disease Fabry disease Phenotype Molecular biology Pedigree alpha-Galactosidase Fabry Disease Female |
| Zdroj: | Human Mutation. 30:1397-1405 |
| ISSN: | 1098-1004 1059-7794 |
| DOI: | 10.1002/humu.21074 |
| Popis: | Fabry disease (alpha-galactosidase A (alpha-Gal A, GLA) deficiency) is a panethnic inborn error of glycosphingolipid metabolism. Because optimal therapeutic outcomes depend on early intervention, a pilot program was designed to assess newborn screening for this disease in 171,977 consecutive Taiwanese newborns by measuring their dry blood spot (DBS) alpha-Gal A activities and beta-galactosidase/alpha-Gal A ratios. Of the 90,288 male screenees, 638 (0.7%) had DBS alpha-Gal A activity30% of normal mean and/or activity ratios10. A second DBS assay reduced these to 91 (0.1%). Of these, 11 (including twins) had5% (Group-A), 64 had 5-30% (Group-B), and 11 had30% (Group-C) of mean normal leukocyte alpha-Gal A activity. All 11 Group-A, 61 Group-B, and 1 Group-C males had GLA gene mutations. Surprisingly, 86% had the later-onset cryptic splice mutation c.936+919GA (also called IVS4+919GA). In contrast, screening 81,689 females detected two heterozygotes. The novel mutations were expressed in vitro, predicting their classical or later-onset phenotypes. Newborn screening identified a surprisingly high frequency of Taiwanese males with Fabry disease (approximately 1 in 1,250), 86% having the IVS4+919GA mutation previously found in later-onset cardiac phenotype patients. Further studies of the IVS4 later-onset phenotype will determine its natural history and optimal timing for therapeutic intervention. |
| Databáze: | OpenAIRE |
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