Prenatal diagnosis of Crigler-Najjar syndrome type I by single-strand conformation polymorphism (SSCP).
Crigler-Najjar syndrome type I (CN-I) is a rare and severe inherited disorder of bilirubin metabolism, caused by the total deficiency of bilirubin-UDP-glucuronosyltransferase (UGT) activity. Enzymatic diagnosis cannot be performed in chorionic villi or amniocytes as UGT is not active in these tissues. The cloning of the UGT1 gene and the identification of disease-causing mutations have led to the possibility of performing DNA-based diagnosis. Here we report DNA-based prenatal diagnosis of CN-I in two Tunisian families in whom CN-I patients were diagnosed. As we had previously shown that CN-I was, in Tunisia, associated with homozygosity for the Q357R mutation within the UGT1 gene, we were able to detect this mutation in both families and to show that it was easily recognized by single-strand conformation polymorphism (SSCP) analysis. In both cases, SSCP analysis of fetal DNA showed that the fetus was heterozygous for the Q357R mutation. In one family, the pregnancy was carried to term and a healthy baby was born, whereas, in the other family, the pregnancy is still continuing. Thus the prenatal diagnosis of CN-I is possible, provided disease-causing mutations have been identified. SSCP analysis of DNA prepared either from amniocytes or from chorionic villi is a simple, reliable and fast method for prenatal diagnosis.
Francoual
Jeanne
J
Laboratoire de Biochimie, Hôpital Antoine Béclère (AP-HP), 92141 Clamart cedex, France.
Trioche
Pascale
P
Mokrani
Chahnez
C
Seboui
Hassen
H
Khrouf
Naïma
N
Chalas
Jacqueline
J
Clement
Marina
M
Capel
Liliane
L
Tachdjian
Gérard
G
Labrune
Philippe
P
D015193:Chorionic Villi Sampling; D003414:Crigler-Najjar Syndrome / Q000175:diagnosis* / Q000235:genetics*; D005260:Female; D014453:Glucuronosyltransferase / Q000235:genetics*; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D009004:Monosaccharide Transport Proteins / Q000235:genetics; D009154:Mutation; D018807:Polymorphism, Single-Stranded Conformational; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods*; D014416:Tunisia; D000099237:UDP-Galactose Translocators; D000099148:UGT1A1 Enzyme
D014453:Glucuronosyltransferase; D009004:Monosaccharide Transport Proteins; D000099237:UDP-Galactose Translocators; D000099148:UGT1A1 Enzyme