title: Mucolipidosis II and III alpha/beta: mutation analysis of 40 Japanese patients showed genotype-phenotype correlation.
abstract: Mucolipidosis (ML) II alpha/beta and III alpha/beta are autosomal recessive diseases caused by a deficiency of alpha and/or beta subunits of the enzyme N-acetylglucosamine-1-phosphotransferase, which is encoded by the GNPTAB gene. We analyzed the GNPTAB gene in 25 ML II and 15 ML III Japanese patients. In most ML II patients, the clinical conditions 'stand alone', 'walk without support' and 'speak single words' were impaired; however, the frequency of 'heart murmur', 'inguinal hernia' and 'hepatomegaly and/or splenomegaly' did not differ between ML II and III patients. We detected mutations in GNPTAB in 73 of 80 alleles. Fourteen new mutations were c.914_915insA, c.2089_2090insC, c.2427delC, c.2544delA, c.2693delA, c.3310delG, c.3388_3389insC+c.3392C>T, c.3428_3429insA, c.3741_3744delAGAA, p.R334L, p.F374L, p.H956Y, p.N1153S and duplication of exon 2. Previously reported mutations were p.Q104X, p.W894X, p.R1189X and c.2715+1G>A causing skipping of exon 13. Homozygotes or compound heterozygotes of nonsense and frameshift mutations contributed to the severe phenotype. p.F374L, p.N1153S and splicing mutations contributed to the attenuated phenotype, although coupled with nonsense mutation. These results show the effective molecular diagnosis of ML II and III and also provide phenotypic prediction. This is the first and comprehensive report of molecular analysis for ML patients of Japanese origin.
authors.affiliation: Department of Pediatrics, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Takanobu
authors.initials: T
authors.lastname: Otomo
authors.forename: Takeshi
authors.initials: T
authors.lastname: Muramatsu
authors.forename: Tohru
authors.initials: T
authors.lastname: Yorifuji
authors.forename: Torayuki
authors.initials: T
authors.lastname: Okuyama
authors.forename: Hiroki
authors.initials: H
authors.lastname: Nakabayashi
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Fukao
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Ohura
authors.forename: Makoto
authors.initials: M
authors.lastname: Yoshino
authors.forename: Akemi
authors.initials: A
authors.lastname: Tanaka
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Okamoto
authors.forename: Koji
authors.initials: K
authors.lastname: Inui
authors.forename: Keiichi
authors.initials: K
authors.lastname: Ozono
authors.forename: Norio
authors.initials: N
authors.lastname: Sakai
mesh_terms: D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D020440:Gene Duplication; D005838:Genotype; D006801:Humans; D008969:Molecular Sequence Data; D009081:Mucolipidoses / Q000201:enzymology* / Q000235:genetics*; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017855:Transferases (Other Substituted Phosphate Groups) / Q000235:genetics*
chemical_list: D017855:Transferases (Other Substituted Phosphate Groups); C030012:UDP-N-acetylglucosamine-lysosomal-enzyme-N-acetylglucosaminephosphotransferase