https://scholars.lib.ntu.edu.tw/handle/123456789/525152
標題: | Fabry disease: incidence of the common later-onset α-galactosidase A IVS4+919G→A mutation in Taiwanese newborns--superiority of DNA-based to enzyme-based newborn screening for common mutations. | 作者: | YIN-HSIU CHIEN NI-CHUNG LEE Chiang S.C. Desnick R.J. WUH-LIANG HWU |
公開日期: | 2012 | 卷: | 18 | 起(迄)頁: | 780-784 | 來源出版物: | Molecular medicine (Cambridge, Mass.) | 摘要: | Fabry disease is a panethnic, X-linked, inborn error of glycosphingolipid metabolism resulting from mutations in the α-galactosidase A gene (GLA) that lead to the deficient activity of the lysosomal enzyme, α-galactosidase A (α-Gal A). Affected males with no α-Gal A activity have the early-onset classic phenotype, whereas those with residual activity present with the later-onset subtype. Recently, we reported that newborn enzyme-based screening using dried blood spots (DBS) in Taiwan revealed a high incidence of newborn males who had the GLA c.936+919G→A (IVS4+919G→A) mutation. This lesion causes cryptic splicing, markedly reducing the amount of wild-type GLA mRNA, and has been found in males with the later-onset Fabry phenotype, manifesting as cardiac, renal and/or cerebrovascular disease. To more accurately determine the incidence of the IVS4+919G→A mutation, 20,063 consecutive newborns were screened by a deoxyribonucleic acid (DNA)-based assay. Of the 10,499 males, 12 (1/875) and 24 of the 9,564 females (1/399) had the mutation. On the basis of these frequencies, the previous newborn enzyme-based DBS screening (cutoff: <30% of the normal mean) only identified 67% and 17% of mutation-positive males and females, respectively. The mean DBS α-Gal A activities in the mutation-positive males and females were 23% (1.54 U) and 55% (3.63 U) of normal mean male/female values, respectively. These studies confirm the high incidence of the IVS4+919G→A mutation in the Taiwanese population and indicate that its detectability by enzyme-based DBS screening is unreliable, especially in females. These studies emphasize the superiority of DNA-based newborn screening for common mutations, particularly for X-linked diseases. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84880616117&doi=10.2119%2fmolmed.2012.00002&partnerID=40&md5=f94c90190a9b2e0ab9006ba4f8e115a9 https://scholars.lib.ntu.edu.tw/handle/123456789/525152 |
ISSN: | 1528-3658 | DOI: | 10.2119/molmed.2012.00002 | SDG/關鍵字: | alpha galactosidase; article; Asian; Fabry disease; female; genetic screening; genetics; human; incidence; male; mutation; newborn; newborn screening; nucleotide sequence; RNA splicing; Taiwan; alpha-Galactosidase; Asian Continental Ancestry Group; DNA Mutational Analysis; Fabry Disease; Female; Genetic Testing; Humans; Incidence; Infant, Newborn; Male; Mutation; Neonatal Screening; RNA Splicing; Taiwan; MLCS; MLOWN |
顯示於: | 醫學系 |
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