UGT1A1 gene mutation due to Crigler-Najjar syndrome in Iranian patients: identification of a novel mutation

Abstract

Crigler-Najjar syndrome (CNS) type I and type II are inherited as autosomal recessive conditions that are caused by mutations in the UGT1A1 gene. We present the analysis of UGT1A1 gene in 12 individuals from three different families. This analysis allowed us to identify one novel mutation, which was not previously described. In this study, three families with clinically diagnosed CNS referred from Khuzestan province, southwest Iran, were screened. After signing the informed consent, peripheral blood samples from the patients and their parents were collected in EDTA-containing tube followed by DNA extraction using a routine phenol-chloroform method. All five coding exons and the flanking intronic regions of the bilirubin-UGT were amplified by polymerase chain reaction (PCR) followed by DNA sequencing by Sanger method. From the first family, a 9-month-old boy was homozygous for a deletion mutation of two adjacent nucleotides including one adenosine (A) and one glutamine (G) between nucleotides 238 and 239 in exon 1 (c.238_240 del AG). In the second family, there were two affected individuals, an 11-year-old girl and a fetus, found to be homozygous for the same mutation. The third family showed a mutation at nucleotide 479 in exon 1 (Val160Glu) that has been reported previously. Molecular analysis can significantly help confirm the diagnosis of CNS, without any need for the liver biopsy, and may help the therapeutic management by ruling out more harmful causes of hyperbilirubinemia.

Figure 1

The family pedigree and sequencing chromatograms of the UGT1A1 gene showing a homozygous two bp deletion (c.238_240delAG, exon 1) in the proband from family A and a heterozygous deletion in the father and the mother of each case; appearance of her chromatogram is comparable to that of a normal control; N, normal.

Figure 2

The family pedigree and sequencing chromatograms of the UGT1A1 gene showing a homozygous two bp deletion (c.238_240delAG, exon 1) in the proband from family B and a heterozygous deletion in the father and the mother of each case; appearance of her chromatogram is comparable to that of a normal control; N, normal.