Abstract
Carbamoyl phosphate synthetase deficiency (CPSD) is an autosomal recessive disorder of ureagenesis. Untreated patients with complete CPSD die as neonates of hyperammonemia. Since CPS is not expressed in amniocytes, prenatal detection is limited to in utero liver biopsy. To determine if the CPS genes are abnormal in affecteds we analyzed nuclear DNA prepared from leukocytes or fibroblasts by hybridization to rat and human CPS cDNA sequences. DNAs from 6 individuals affected with CPSD, 2 non-affected sibs and 2 controls were digested with Eco RI, Hind III or Pst I and hybridized to 32P labeled rat CPS cDNA. No variations in the number or size of hybridizing fragments were seen. To enable linkage studies DNAs from the 10 parents were digested with 12 different restriction endonucleases. Only after Bgl I digestion was a variation seen (23,15.5 and 13 kb bands in some versus 23 kb in others). Using a smaller human CPS cDNA we detected three patterns 23, 23+13 and 13 kb. In one family both parents had the 23+13, 2 affected sibs had only the 23 and a normal sib had only the 13 kb fragment(s) in agreement with simple Mendelian inheritance. In 2 other families the affected had only the 23 kb fragment. The affected children in the remaining 2 families had 23+13 or 13 kb patterns. Our studies suggest that 1) large deletions or insertions of the CPS genes were not detected; 2) the CPSD phenotype and the Bql I derived restriction fragments co-segregate and 3) genetic heterogeneity exists in CPSD.
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Mallonee, R., Fearon, E., III, J. et al. CARBAMOYL PHOSPHATE SYNTHETASE DEFICIENCY: DNA ANALYSIS. Pediatr Res 18 (Suppl 4), 296 (1984). https://doi.org/10.1203/00006450-198404001-01219
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DOI: https://doi.org/10.1203/00006450-198404001-01219