Stone R L, Aimi J, Barshop B A, Jaeken J, Van den Berghe G, Zalkin H, Dixon J E
Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor 48109-0606.
Nat Genet. 1992 Apr;1(1):59-63. doi: 10.1038/ng0492-59.
We have examined the molecular basis of three cases of severe mental retardation with autistic features in one family. A point mutation in a purine nucleotide biosynthetic enzyme, adenylosuccinate lyase (ASL), segregates with the disorder. The affected children are homozygous for the point mutation while the parents and all four unaffected children are heterozygous. The point mutation is absent in control subjects. The point mutation results in a Ser413Pro substitution which leads to structural instability of the recombinant mutant enzyme, and this instability lowers ASL levels in lymphocytes. These observations suggest that the instability of ASL underlies the severe developmental disorder in the affected children, and that mutations in the ASL gene may result in other cases of mental retardation and autistic features.
