BSEP及FIC1基因在新生兒肝炎及正常嬰兒之變異及表現

Background/Aim: FIC1 and BSEP mutations have
recently been found to cause progressive familial
intrahepatic cholestasis (PFIC). Mutations in both
genes have not been reported in Asian children. We
had identified novel mutations in FIC1 and BSEP
genes in 80% of Taiwanese infants with sporadic
progressive intrahepatic cholestasis. This study is to
elucidate the different expression levels of BSEP and
other canalicular transporters in different fetal and
postnatal ages, and to determine the role of FIC1 and
BSEP mutations in children with neonatal hepatitis in
Taiwan.
Methods and Results: In the first part we examined the
expression levels of fetal, neonatal, and adult livers by
semi-quantitative RT-PCR. We found that BSEP and
other transporters were expressed as early as 16 weeks
of gestational age, and became strongly expressed
after 20 weeks. This finding is compatible with the
time when bile starts to flow from liver to intestine.
We also determined the serum bile acid levels in
normal newborn infants and found that normal
newborn have serum bile acid below 94mmole/L, much
higher that adults, which was below 10 mmole/L. In
the second part we sequenced the entire coding
sequences of BSEP in 5 patients and FIC1 in 2
patients with neonatal hepatitis. We found no mutation
in these patients. Immunohistochemical staining in the
liver tissue of neonatal hepatitis patients showed
positive results.
Discussion: Our study provided the first data on the
expression levels of liver canalicular transporters in
human fetal and postnatal periods. This data helps to
elucidate the neonatal bile physiology. In addition, we
found no evidence that genetic alternations occurred in
benign neonatal hepatitis.