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A homozygous mutation in a Chinese man with Crigler–Najjar syndrome type II and a family genetic analysis
Author(s) -
WU Jian Xin,
CHENG Guang Yu,
HUANG Jian
Publication year - 2008
Publication title -
journal of digestive diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.684
H-Index - 51
eISSN - 1751-2980
pISSN - 1751-2972
DOI - 10.1111/j.1751-2980.2008.00328.x
Subject(s) - proband , missense mutation , exon , genetics , medicine , mutation , compound heterozygosity , gene , microbiology and biotechnology , biology
OBJECTIVE: To investigate the family genetic background of a 22‐year‐old man with Crigler–Najjar syndrome type II (CN‐II). METHODS: After the proband (patient) with CN‐II was diagnosed by liver function tests, a low calorie intake test and an oral phenobarbital enzyme‐induction trial, blood samples were collected from 11 family members for identifying DNA gene groups. Exons 1–5 of the UGT1A1 gene were amplified by polymerase chain reaction (PCR) and mutations of the UGT1A1 gene were screened by a direct DNA sequencing. RESULTS: The serum unconjugated bilirubin increased in the proband from 156.4 µmol/L to 243.5 µmol/L after he started a low calorie intake, and it decreased to 51.8 µmol/L within a month of taking oral phenobarbital daily. Both functional tests and ultrasonographic images of the liver were normal except for the unconjugated hyperbilirubinemia. A missense mutation of Tyr486Asp at exon 5 in the UGT1A1 gene and a homozygous mutation were confirmed in the proband. Heterozygous mutations were found in his parents, his younger sister and three great‐uncles, while no mutation of the UGT1A1 gene was detected in the remaining four family members. CONCLUSION: A missense mutation of Tyr486Asp is considered to be the cause of the CN‐II in this patient. It is a recessive trait that is autosomally inherited in this family. No influence of the mutation was found on the response elements for phenobarbital in the promoter region.