GLYCOGENOSIS TYPE-II - A JUVENILE-SPECIFIC MUTATION WITH AN UNUSUAL SPLICING PATTERN AND A SHARED MUTATION IN AFRICAN-AMERICANS

The recessively inherited deficiency of acid alpha-glucosidase (GAA) c alled Glycogenosis Type II is expressed as three different phenotypes: infantile, juvenile, and adult. At the molecular level, infantile and adult forms of the disease have been extensively studied, but little is known regarding the genetic defects associated with the juvenile fo rm. We describe a novel mutation that defines the intermediate juvenil e phenotype in a compound heterozygous patient. A transversion of t to g in intron 6 at position -22 creates a cryptic acceptor site and res ults in unusual splicing abnormality: insertion of 21 nucleotides of t he intronic sequence into mRNA and removal of exon 6 without disruptio n of the reading frame. The second mutation, Arg854Stop in exon 18, ha d been previously identified in another African-American patient (Herm ans et al., 1993a). Family study indicates that a silent allele harbor ing the Arg854Stop mutation in our patient is inherited from the patie nt's father who is also African American, thus suggesting a common mut ation in this population. (C) 1997 Wiley-Liss, Inc.(dagger).