A DE-NOVO 13-NT DELETION, A NEWLY IDENTIFIED C647W MISSENSE MUTATION AND A DELETION OF EXON-18 IN INFANTILE ONSET GLYCOGEN-STORAGE-DISEASE TYPE-II (GSDII)
Ml. Huie et al., A DE-NOVO 13-NT DELETION, A NEWLY IDENTIFIED C647W MISSENSE MUTATION AND A DELETION OF EXON-18 IN INFANTILE ONSET GLYCOGEN-STORAGE-DISEASE TYPE-II (GSDII), Human molecular genetics, 3(7), 1994, pp. 1081-1087
We identified the presumably rare event of de novo mutation in an auto
somal recessive disorder, glycogen storage disease type II (GSDII). GS
DII results from inherited deficiency of acid alpha-glucosidase (acid
maltase) and both the expressed and structural gene (designated GAA) h
ave been isolated. The mutation was a deletion of 13 nt of coding sequ
ence (Delta nt 1456-1468) on the paternally derived allele of the prob
and. The Delta nt 1456-1468 results in a reading frameshift and a prem
ature termination signal upstream of the enzyme catalytic site. Patern
ity was confirmed by presence of two downstream, uncommon amino acid s
ubstitutions (E689K, W746C) in both proband and father and by comparis
on of nine short tandem repeats. The maternal allele carried a newly i
dentified deleterious C647W missense mutation in a highly conserved ar
ea of the protein. The C647W mutation was also found in a second unrel
ated proband, heteroallelic with a deletion extending from IVS17 to IV
S18.