title: Prevalence of c.1559delT in ALPL, a common mutation resulting in the perinatal (lethal) form of hypophosphatasia in Japanese and effects of the mutation on heterozygous carriers.
abstract: Hypophosphatasia (HPP) is an inherited disorder caused by mutations in ALPL that encodes an isozyme of alkaline phosphatase (ALP), TNSALP. One of the most frequent ALPL mutations is c.1559delT, which causes the most severe HPP, the perinatal (lethal) form (pl-HPP). c.1559delT has been found only in Japanese and its prevalence is suspected to be high; however, the allele frequency of c.1559delT in Japanese remains unknown. We designed a screening system for the mutation based on high-resolution melting curve analysis, and examined the frequency of c.1559delT. We found that the c.1559delT carrier frequency is 1/480 (95% confidence interval, 1/1562-1/284). This indicates that ∼1 in 900 000 individuals to have pl-HPP caused by a homozygous c.1559delT mutation. In our analysis, the majority of c.1559delT carriers had normal values of HPP biochemical markers, such as serum ALP and urine phosphoethanolamine. Our results indicate that the only way to reliably detect whether individuals are pl-HPP carriers is to perform the ALPL mutation analysis.
authors.affiliation: Division of Clinical Genetics, Nippon Medical School Hospital, Tokyo, Japan. aw3703@nms.ac.jp
authors.forename: Atsushi
authors.initials: A
authors.lastname: Watanabe
authors.forename: Tatsuki
authors.initials: T
authors.lastname: Karasugi
authors.forename: Hideaki
authors.initials: H
authors.lastname: Sawai
authors.forename: Banyar Than
authors.initials: BT
authors.lastname: Naing
authors.forename: Shiro
authors.initials: S
authors.lastname: Ikegawa
authors.forename: Hideo
authors.initials: H
authors.lastname: Orimo
authors.forename: Takashi
authors.initials: T
authors.lastname: Shimada
mesh_terms: D000469:Alkaline Phosphatase / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D005820:Genetic Testing; D006579:Heterozygote; D006801:Humans; D007014:Hypophosphatasia / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D009154:Mutation; D015995:Prevalence
chemical_list: C548267:ALPL protein, human; D000469:Alkaline Phosphatase