The Lab. of Genetics and Metabolism, Hunan Children's Research Institute (HCRI), Hunan Children's Hospital, University of South China, Changsha, China.
Gene. 2013 Apr 15;518(2):467-9. doi: 10.1016/j.gene.2013.01.020. Epub 2013 Jan 24.
Alkaptonuria (AKU) is one of the first prototypic inborn errors in metabolism and the first human disease found to be transmitted via Mendelian autosomal recessive inheritance. It is caused by HGD mutations, which leads to a deficiency in homogentisate 1,2-dioxygenase (HGD) activity. To date, several HGD mutations have been identified as the cause of the prototypic disease across different ethnic populations worldwide. However, in Asia, the HGD mutation is very rarely reported. For the Chinese population, no literature on HGD mutation screening is available to date. In this paper, we describe two novel HGD mutations in a Chinese AKU family, the splicing mutation of IVS7+1G>C, a donor splice site of exon 7, and a missense mutation of F329C in exon 12. The predicted new splicing site of the mutated exon 7 sequence demonstrated a 303bp extension after the mutation site. The F329C mutation most probably disturbed the stability of the conformation of the two loops critical to the Fe(2+) active site of the HGD enzyme.
尿黑酸尿症（AKU）是最早发现的代谢性先天性缺陷疾病之一，也是首个被证实通过孟德尔常染色体隐性遗传方式传播的人类疾病。该疾病由 HGD 基因突变引起，导致 HOMOGENTISATE 1,2-DIOXYGENASE（HGD）活性缺乏。迄今为止，已在全球不同种族人群中发现了多种 HGD 突变，可导致该典型疾病。然而，在亚洲，HGD 突变非常罕见。对于中国人群，目前尚无关于 HGD 突变筛查的文献报道。在本文中，我们描述了一个中国 AKU 家系中的两个新的 HGD 突变，分别为内含子 7 的剪接突变 IVS7+1G>C 和外显子 12 的错义突变 F329C。突变外显子 7 序列的新预测剪接位点在突变部位后延伸了 303bp。F329C 突变很可能破坏了 HGD 酶的两个关键环的构象稳定性，这两个环对 Fe(2+)活性位点至关重要。
