The genetic inheritance of Gibert's syndrome

吉尔伯特综合征患者有轻微的慢性高未结合胆红素血症。根据血液中的胆红素水平，估计有3%到10%的普通人群患有吉尔伯特综合征。在吉尔伯特综合征患者中，肝脏的葡萄糖醛酸化活性对于有效的胆红素排泄是必不可少的，大约是正常的30%。遗传分析表明，Gilbert综合征患者胆红素：UDP-葡萄糖醛酸基转移酶基因存在杂合性突变(Aono et al，345,958-959,1995)，提示为显性遗传。另一方面，Bosma et al.(新引擎。J.Med，333,1171-1175,1995)报道了吉尔伯特综合征患者基因启动子区的纯合子异常(TATA盒中的额外TA)，表明该综合征具有隐性特征。为了阐明Gilbert综合征的遗传机制，我们对患者及其家属进行了进一步的遗传分析。到目前为止，所有接受检查的女性患者都在这两个等位基因上都有异常。一些男性患者也存在这两个等位基因的异常。然而，足够有趣的是，其余的男性患者只在两个等位基因中都有异常。这些结果提示，除基因异常外，其他因素(S)也是该综合征在男性完全表现所必需的。

Patients with Gilbert's syndrome have mild, chronic unconjugated hyperbilirubinemia. Based on the bilirubin level in the blood, 3 to 10 percent of the general population are estimated to have Gilbert's syndrome. Hepatic glucuronidating activity, which is essential for efficient biliary excretion of bilirubin, is approximately 30 percent of normal in patients with Gilbert's syndrome. Genetic analysis showed that heterozygous mutation in bilirubin : UDP-glucuronosyltransferase gene was observed in patients with Gilbert's syndrome (Aono et al, Lancet, 345, 958-959, 1995), suggesting the dominant trait of inheritance. On the other hand, Bosma et al. (New Engl. J.Med., 333, 1171-1175, 1995) reported a homozygous abnormality in the promoter region of the gene (extra TA in TATA box) in patients with Gilbert's syndrome, indicating the recessive trait of the syndrome. In order to clarify the mechanism underlying the genetic inheritance of Gilbert's syndrome, we carried out a futther genetic analysis of patients and their families. All female patients so far examined had abnormalities on the both alleles. Some male patients also had abnormalities on the both alleles. However, interestingly enough, the rest of the male patients had abnormalities only in either allele. These findings suggest that other factor(s) besides the gene abnormality is necessary for the complete manifestation of the syndrome in male.