Homocystinuria in Taiwan: an inordinately high prevalence in an Austronesian aboriginal tribe, Tao.

Abstract

The newborn screening of homocystinuria in Taiwan has never been formally reported before. Since 1984, out of 5 million newborns screened, only 3 newborns (Han Taiwanese) suffering from homocystinuria were detected in this newborn screening program. Four mutations (p.R121L [c.362G>T], p.E176K [c.526G>A], p.V320G [c.959T>G] and p.G259D [c.776G>A]) were identified in these 3 patients. Unexpectedly, we recently found 8 patients presenting with homocystinuria in an Austronesian Taiwanese Tao tribe. Out of them, three patients participated in the newborn screening program but were unidentified by the current newborn homocystinuria (using methionine as a marker) screening. All the Tao patients are homozygous for a new p.D47E (c.141T>A) mutation. Among the 428 adult islanders screened for the D47E mutation, approximately 1 in 7.78 is a carrier of the mutation, and an estimated 1 in 240 islanders suffered from homocystinuria. This is the highest known prevalence of homocystinuria worldwide. The result of expression studies of all the mutations identified in Taiwan revealed that, except for p.D47E mutation, all mutations were severely limited in their ability to form functional tetramers. The clinical manifestations of the Tao patients varied widely, despite sharing the same mutation and very similar genetic and environmental backgrounds. Comparisons of clinical and biochemical phenotypes of these patients were presented in this report.

• Authors: Yung-Hsiu Lu, Yu-Hsiu Huang, Li-Mei Cheng, Hsiao-Chi Yu, Ju-Hui Hsu, Tina Jui-Ting Wu, Ming-Yu Lo, Andrew Lin, Ching-Yuang Lin, Jer-Yuarn Wu, Dau-Ming Niu
• Journal: Molecular genetics and metabolism (Mol Genet Metab) Vol. 105 Issue 4 Pg. 590-5 (Apr 2012) ISSN: 1096-7206 [Electronic] United States
• PMID: 22353391 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Inc. All rights reserved.

Chemical References

• Cystathionine beta-Synthase

Topics

• Adolescent
• Adult
• Blotting, Western
• Cells, Cultured
• Child
• Cystathionine beta-Synthase (genetics)
• DNA Mutational Analysis
• Fibroblasts (cytology, enzymology)
• Heterozygote
• Homocystinuria (diagnosis, epidemiology, genetics)
• Homozygote
• Humans
• Infant, Newborn
• Mutagenesis, Site-Directed
• Mutation (genetics)
• Neonatal Screening
• Prevalence
• Real-Time Polymerase Chain Reaction
• Taiwan (epidemiology)