title: Genetic approach to prenatal diagnosis in urea cycle defects.
abstract: OBJECTIVE
  To demonstrate the feasibility of prenatal diagnosis by molecular genetics in all urea cycle defects in order to improve and standardize the current approaches.
  
  
  METHODS
  Deceased index patients who had suffered from a urea cycle disorder were investigated for mutations of the biochemically most likely affected gene. If no material of index patients was available, parental DNA was studied for obligate carrier status. Fetal cells of 15 pregnancies, either chorionic villi or amniotic fluid cells, were used for direct sequence analysis of the respective mutations. Thirteen families were investigated, of which two were affected by N-acetylglutamate synthase deficiency, four by carbamoylphosphate synthetase 1 deficiency, one by ornithine transcarbamylase deficiency, three by argininosuccinate synthetase deficiency, two by argininosuccinate lyase deficiency, and one by arginase deficiency.
  
  
  RESULTS
  Molecular genetics allowed the determination of the fetal status in all cases. Besides 14 known mutations, we detected the novel mutation c.544delC of the N-acetylglutamate synthase gene, the novel missense mutation c.721G>A (E241K) of the argininosuccinate lyase gene, and the novel double mutated allele comprising the known mutation c.703G>A (G235R) and the novel insertion c.712ins[GGACC](2) (254X) of the arginase 1 gene.
  
  
  CONCLUSIONS
  Direct genetic analysis of chorionic villi or amniotic fluid cells is feasible, fast, and specific, and can be regarded as the method of choice for prenatal diagnosis in urea cycle disorders.
authors.affiliation: Universitätsklinikum Münster, Klinik und Poliklinik für Kinderheilkunde, Münster, Germany. haeb@uni-muenster.de
authors.forename: Johannes
authors.initials: J
authors.lastname: Häberle
authors.forename: Hans Georg
authors.initials: HG
authors.lastname: Koch
mesh_terms: D000123:Acetyltransferases / Q000172:deficiency; D051046:Amino-Acid N-Acetyltransferase; D001124:Argininosuccinate Synthase / Q000172:deficiency; D056807:Argininosuccinic Aciduria; D002222:Carbamoyl-Phosphate Synthase (Ammonia) / Q000172:deficiency; D015193:Chorionic Villi Sampling; D005260:Female; D005820:Genetic Testing; D006801:Humans; D020162:Hyperargininemia; D008661:Metabolism, Inborn Errors / Q000175:diagnosis* / Q000235:genetics; D020163:Ornithine Carbamoyltransferase Deficiency Disease; D011247:Pregnancy; D011296:Prenatal Diagnosis; D014508:Urea / Q000378:metabolism*
chemical_list: D014508:Urea; D000123:Acetyltransferases; D051046:Amino-Acid N-Acetyltransferase; C494874:NAGS protein, human; D002222:Carbamoyl-Phosphate Synthase (Ammonia); D001124:Argininosuccinate Synthase