First report of HGD mutations in a Chinese with alkaptonuria.
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.
The Lab. of Genetics and Metabolism, Hunan Children's Research Institute (HCRI), Hunan Children's Hospital, University of South China, Changsha, China.
Yong-jia
YJ
Yang
Ji-hong
JH
Guo
Wei-jian
WJ
Chen
Rui
R
Zhao
Jin-song
JS
Tang
Xiao-hua
XH
Meng
Liu
L
Zhao
Ming
M
Tu
Xin-yu
XY
He
Ling-qian
LQ
Wu
Yi-min
YM
Zhu
D000474:Alkaptonuria / Q000175:diagnosis / Q000235:genetics*; D000595:Amino Acid Sequence; D044466:Asian People / Q000235:genetics; D002681:China; D005091:Exons; D005260:Female; D050560:Homogentisate 1,2-Dioxygenase / Q000737:chemistry / Q000172:deficiency* / Q000235:genetics*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D020125:Mutation, Missense; D009690:Nucleic Acid Conformation; D010641:Phenotype
D050560:Homogentisate 1,2-Dioxygenase