title: Different attenuated phenotypes of GM2 gangliosidosis variant B in Japanese patients with HEXA mutations at codon 499, and five novel mutations responsible for infantile acute form.
abstract: Eight mutations of the alpha subunit of beta-hexosaminidase A gene ( HEXA) were identified in eight patients with GM2 gangliosidosis variant B. They were five missense mutations, two splice-site mutations, and one two-base deletion. Five of them, R252L (CGT-->CTT), N295S (AAT-->AAC), W420C (TGG-->TGT), IVS 13, +2A-->C, and del 265-266AC (exon 2), were novel mutations responsible for infantile acute form of GM2 gangliosidosis. Two missense mutations, R499H and R499C, were found in one allele of two patients with attenuated phenotypes. The patient with R499C showed a late infantile form, and the other patient with R499H showed a juvenile form. These two mutations have been reported previously in the patients of other ethnic groups, and they have been known to cause attenuated phenotypes. The milder phenotypes of GM2 gangliosidosis variant B, different from the infantile acute form, have not been reported so far in Japan, and this is the first report of Japanese patients with attenuated phenotypes and their molecular analysis.
authors.affiliation: Department of Pediatrics, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan. akemi-chan@med.osaka-cu.ac.jp
authors.forename: Akemi
authors.initials: A
authors.lastname: Tanaka
authors.forename: Lan Thi Ngcok
authors.initials: LT
authors.lastname: Hoang
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Nishi
authors.forename: Satoshi
authors.initials: S
authors.lastname: Maniwa
authors.forename: Makio
authors.initials: M
authors.lastname: Oka
authors.forename: Tsunekazu
authors.initials: T
authors.lastname: Yamano
mesh_terms: D000208:Acute Disease; D044466:Asian People / Q000235:genetics; D002648:Child; D003062:Codon; D005260:Female; D054818:Hexosaminidase A; D006801:Humans; D007223:Infant; D008297:Male; D020125:Mutation, Missense; D010641:Phenotype; D013661:Tay-Sachs Disease / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D001619:beta-N-Acetylhexosaminidases / Q000235:genetics*
chemical_list: D003062:Codon; D054818:Hexosaminidase A; D001619:beta-N-Acetylhexosaminidases