Prenatal diagnosis in adenylosuccinate lyase deficiency.
Adenylosuccinate lyase deficiency, an autosomal recessive inborn error of purine synthesis, provokes accumulation in body fluids of succinylaminoimidazolecarboxamide riboside and succinyladenosine, the dephosphorylated derivatives of the two substrates of the enzyme. Most patients display severe psychomotor retardation, often accompanied by epilepsy and/or autistic features, although some are only mildly retarded. About 20 mutations are known. Prenatal diagnosis was performed twice on chorion villi of the mother of a previously diagnosed patient with a C5T mutation (exon 1) on the maternal allele, and a C1185A mutation (exon 11) on the paternal allele. Both suppress a Fnu4HI restriction site. In a first fetus, incubation of PCR products generated from genomic DNA of exon 1 with Fnu4HI yielded a 113 bp fragment from a control and the father's gene, and both a 113 bp and 170 bp fragment from the mother, affected sibling and fetus. Incubation of PCR products of exons 11-12 with Fnu4HI yielded a 550 bp fragment from a control and the mother's gene, and a 550 bp and 600 bp fragment from the father, affected sibling and fetus. Assay of adenylosuccinate lyase on the aborted fetal liver confirmed the enzyme deficiency. A second fetus displayed only the maternal mutation.
Marie
S
S
Laboratory of Physiological Chemistry, Christian de Duve Institute of Cellular Pathology and University of Louvain Medical School, Brussels, Belgium.
Flipsen
J W
JW
Duran
M
M
Poll-The
B T
BT
Beemer
F A
FA
Bosschaart
A N
AN
Vincent
M F
MF
Van den Berghe
G
G
D000028:Abortion, Induced; D000264:Adenylosuccinate Lyase / Q000172:deficiency* / Q000235:genetics; D000653:Amniotic Fluid / Q000737:chemistry; D002478:Cells, Cultured; D015193:Chorionic Villi Sampling; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000032:analysis / Q000378:metabolism; D015252:Deoxyribonucleases, Type II Site-Specific / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000737:chemistry; D006801:Humans; D008099:Liver / Q000201:enzymology; D009154:Mutation; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011296:Prenatal Diagnosis; D011687:Purines / Q000032:analysis / Q000378:metabolism
D011687:Purines; D004247:DNA; C069758:endodeoxyribonuclease Fnu4HI; D015252:Deoxyribonucleases, Type II Site-Specific; D000264:Adenylosuccinate Lyase