Compound heterozygous patient with glycogen storage disease type III: identification of two novel AGL mutations, a donor splice site mutation of Chinese origin and a 1-bp deletion of Japanese origin.
Glycogen storage disease type III (GSD III) is an autosomal recessive disorder caused by deficiency of glycogen-debranching enzyme (AGL). We studied a 2-year-old GSD III patient whose parents were from different ethnic groups. Nucleotide sequence analysis of the patient showed two novel mutations: a single cytosine deletion at nucleotide 2399 (2399delC) in exon 16, and a G-to-A transition at the +5 position at the donor splice site of intron 33 (IVS33+5G>A). Analysis of the mRNA produced by IVS33+5G>A showed aberrant splicing: skipping of exon 33 and activation of a cryptic splice site in exon 34. Mutational analysis of the family revealed that the 2399delC was inherited from her father, who is of Japanese origin, and the IVS33+5G>A from her mother, who is of Chinese descent, establishing that the patient was a compound heterozygote. To our knowledge, this is the first report of a mutation identified in a GSD III patient from the Chinese population.
Department of Endocrinology and Metabolism, Toranomon Hospital and Okinaka Memorial Institute for Medical Research, Tokyo, Japan. QFG00550@nifty.ne.jp
M
M
Okubo
A
A
Horinishi
Y
Y
Suzuki
T
T
Murase
K
K
Hayasaka
D002675:Child, Preschool; D002681:China; D004252:DNA Mutational Analysis; D018076:DNA, Complementary / Q000378:metabolism; D005091:Exons; D005192:Family Health; D005260:Female; D005819:Genetic Markers; D006004:Glycogen Debranching Enzyme System / Q000172:deficiency / Q000235:genetics*; D006010:Glycogen Storage Disease Type III / Q000235:genetics*; D006239:Haplotypes; D006579:Heterozygote; D006801:Humans; D007438:Introns; D007564:Japan; D008297:Male; D008957:Models, Genetic; D009154:Mutation; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012326:RNA Splicing; D012333:RNA, Messenger / Q000378:metabolism
D018076:DNA, Complementary; D005819:Genetic Markers; D006004:Glycogen Debranching Enzyme System; D012333:RNA, Messenger