Tohoku J. Exp. Med., 2018 December, 246(4)

A Putative Mutation Hotspot of the AGXT Gene Associated with Primary Hyperoxaluria Type 1 in the Chinese Population

XIYUAN LI,1 JIE GU,2 YANLING YANG,3 JUN LI4 and YANHAN LI2

1Precision Medicine Center, General Hospital of Tianjin Medical University, Tianjin, China
2Department of Laboratory Animal Center, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China
3Department of Pediatrics, Peking University First Hospital, Beijing, China
4Department of Urology, Beijing Friendship Hospital, Capital Medical University, Beijing, China

Primary hyperoxaluria type 1 (PH1), a rare autosomal recessive disorder, is characterized by renal stones, nephrocalcinosis, and chronic kidney disease. PH1 is caused by defects in alanine glyoxylate aminotransferase (AGT, 392 amino-acid residues), which is encoded by the alanine-glyoxylate and serine-pyruvate aminotransferase (AGXT) gene. This study aimed to determine the clinical, biochemical, and mutation spectrum of patients with PH1 from mainland China. Four patients (two adults and two children, age range: 1 to 34 years) from four unrelated families were admitted because of kidney stones. The adult patients had chronic kidney disease, while the pediatric patients retained the normal kidney function. Four mutations of the AGXT gene were detected, including one novel mutation, c.1015delG (p.V339Sfs*2). One adult male with late-onset PH1 is a compound heterozygote of the c.815_816insGA (p.S275Rfs*38) and c.1015delG (p.V339Sfs*2) mutations. These frame-shift mutations could result in the production of truncated AGT proteins. Other patients include an adult female who is heterozygous for c.473C>T (p.S158L) and c.815_816insGA mutations and two boys that are respectively homozygous for the c.815_816insGA mutation and for the c.614C>T (p.S205L) mutation. Thus, the c.815_816insGA mutation accounts for 4/8 alleles in the present study; importantly, the position c.815 represents the 5'-end of the consecutive wild-type sequence of GAGAGAGA. In conclusion, we describe one novel mutation, c.1015delG, and a common mutation, c.815_816insGA, of the AGXT gene among four unrelated families with PH1. Moreover, we suggest that the short repeat of the GA dinucleotide may represent a mutation hotspot in the Chinese population.

Key words —— alanine glyoxylate aminotransferase; alanine-glyoxylate and serine-pyruvate aminotransferase; kidney stones; plasma and urine oxalate; primary hyperoxaluria type 1

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Tohoku J. Exp. Med., 2018, 246, 233-241

Correspondence: Yanhan Li, M.D., Ph.D., Department of Laboratory Animal Center, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 288 Nanjing Road, Heping District, Tianjin 300020, China.

e-mail: yanhanli5@126.com

Jun Li, M.D., Ph.D., Department of Urology, Beijing Friendship Hospital, Capital Medical University, No. 95 Yongan Road, Xicheng District, Beijing 100069, China.

e-mail: lijun_bjfh@126.com

Yanling Yang, M.D., Ph.D., Department of Pediatrics, Peking University First Hospital, No. 1 Xiamen Street, Xicheng District, Beijing 100034, China.

e-mail:organic_acid@126.com