Identification of a new point mutation in hypoxanthine phosphoribosyl transferase responsible for hyperuricemia in a female patient.
A 29-year-old woman was referred to our department because of gout. Routine laboratory data showed hyperuricemia, a high level of plasma oxypurines, increased urinary uric acid excretion, and increased urinary oxypurine excretion, with decreased hypoxanthine phosphoribosyl transferase (HPRT) activity in the erythrocytes. From these findings, the patient was diagnosed with a partial deficiency of HPRT. To determine its properties, a cDNA sequence encoding HPRT and the androgen receptor AR XIST minimal promoter gene, as well as methylation of the AR gene were investigated. The HPRT cDNA sequence revealed a point mutation of G to A in nucleotide 40, which changed codon 14 from GAA (Glu) to AAA (Lys) in the mutant gene. In addition, the HPRT genomic DNA sequence, including the mutation site, revealed the same point mutation, indicating that the patient was heterozygote. Further analysis of the AR gene on the X chromosome suggested nonrandom X-chromosome inactivation, whereas the AR XIST minimal promoter gene was normal. Such results have not been previously reported in a female with partial HPRT deficiency.
Inokuchi
Taku
T
Department of Internal Medicine, Hyogo College of Medicine, Hyogo 663-8501, Japan.
Moriwaki
Yuji
Y
Takahashi
Sumio
S
Tsutsumi
Zenta
Z
Ka
Tuneyoshi
T
Yamamoto
Asako
A
Cheng
Jidong
J
Hashimoto-Tamaoki
Tomoko
T
Hada
Toshikazu
T
Yamamoto
Tetsuya
T
D000241:Adenosine; D000328:Adult; D018076:DNA, Complementary / Q000032:analysis; D005260:Female; D018698:Glutamic Acid / Q000235:genetics; D006147:Guanine; D006801:Humans; D033461:Hyperuricemia / Q000201:enzymology* / Q000235:genetics*; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics*; D008239:Lysine / Q000235:genetics; D017354:Point Mutation; D017422:Sequence Analysis, DNA
D018076:DNA, Complementary; D018698:Glutamic Acid; D006147:Guanine; D007041:Hypoxanthine Phosphoribosyltransferase; D008239:Lysine; D000241:Adenosine