Prenatal diagnosis of progressive familial intrahepatic cholestasis type 2.
OBJECTIVE
Progressive familial intrahepatic cholestasis type 2 (PFIC2) results from genetic defects of the hepatobiliary bile salt export pump (BSEP, ABCB11) at chromosome 2q24. Patients with progressive cholestasis and liver cirrhosis usually need liver transplantation in the first decade. Mutations in ABCB11 are also associated with benign recurrent intrahepatic cholestasis type 2 and intrahepatic cholestasis of pregnancy in adult patients. We aimed to make the prenatal diagnosis of PFIC2.


METHODS
Genetic diagnosis was performed by genomic DNA analysis. Prenatal genetic diagnosis was made by fetal amniotic DNA and chorionic DNA analysis.


RESULTS
We report on two families of PFIC2 with inherited compound heterozygous mutations of ABCB11 (M183V and R303K in Family 1, V284L and 1145delC in Family 2) from the parents. An infant with heterozygous M183V mutation was later born healthy in Family 1. A fetus with compound heterozygous missense mutation V284L and 1145delC was terminated in Family 2.


CONCLUSIONS
Prenatal diagnosis of PFIC2 was helpful to prevent further affected children in families with this fatal disease.
Department of Pediatrics, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
Szu-Ta
ST
Chen
Huey-Ling
HL
Chen
Yi-Ning
YN
Su
Yu-Jung
YJ
Liu
Yen-Hsuan
YH
Ni
Hong-Yuan
HY
Hsu
Chia-Shiang
CS
Chu
Nai-Yu
NY
Wang
Mei-Hwei
MH
Chang
D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000028:Abortion, Induced; D000649:Amniocentesis; D002780:Cholestasis, Intrahepatic / Q000175:diagnosis* / Q000235:genetics; D015193:Chorionic Villi Sampling; D004252:DNA Mutational Analysis; D018450:Disease Progression; D017809:Fatal Outcome; D005260:Female; D005820:Genetic Testing; D006579:Heterozygote; D006801:Humans; D007231:Infant, Newborn; D050498:Live Birth; D008297:Male; D009154:Mutation; D010375:Pedigree; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods*
C093491:ABCB11 protein, human; D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters