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

Am J Med Genet. 2000 Jul 31;93(3):211-4. doi: 10.1002/1096-8628(20000731)93:3<211::aid-ajmg10>3.0.co;2-z.

Abstract

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.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Child, Preschool
  • China
  • DNA Mutational Analysis
  • DNA, Complementary / metabolism
  • Exons
  • Family Health
  • Female
  • Genetic Markers
  • Glycogen Debranching Enzyme System / deficiency
  • Glycogen Debranching Enzyme System / genetics*
  • Glycogen Storage Disease Type III / genetics*
  • Haplotypes
  • Heterozygote*
  • Humans
  • Introns
  • Japan
  • Male
  • Models, Genetic
  • Mutation*
  • Point Mutation
  • Polymerase Chain Reaction
  • Polymorphism, Genetic
  • RNA Splicing*
  • RNA, Messenger / metabolism

Substances

  • DNA, Complementary
  • Genetic Markers
  • Glycogen Debranching Enzyme System
  • RNA, Messenger