Diverse point mutations result in glucose-6-phosphate dehydrogenase (G6PD)
polymorphism in Taiwan
TK Tang, CS Huang, MJ Huang, KB Tam, CH Yeh and CJ Tang
Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan, Republic
of China.
Glucose-6-PHOSPHATE dehydrogenase (G6PD; EC 1.1.1.49) deficiency is the
most common human enzymopathy, affecting more than 200 million people
worldwide. Although greater than 400 variants have been described based on
clinical and biochemical criteria, little is known about the molecular
basis of these G6PD deficiencies. Recently, the gene that encodes human
G6PD has been cloned and sequenced, which enables us to examine directly
the heterogeneity of G6PD at the DNA level. During the past 10 years, we
examined the G6PD activity in 21,271 newborn Chinese infants (11,400 males
and 9,871 females) and identified 314 (2.8%) males and 246 (2.5%) females
having low G6PD activity. The G6PD gene from 10 randomly selected affected
individuals and their relatives was polymerase chain reaction (PCR)
amplified, subcloned, and sequenced. Our results indicate that at least
four types of mutation are responsible for the G6PD polymorphism in Taiwan.
The first type of mutation (487 G----A) was found in an affected Chinese
with a G to A change at nucleotide 487, which results in a (163)Gly to Ser
substitution. The second type of mutation (493 A----G) is a novel mutation
that has not been reported in any other ethnic group and was identified in
two affected Chinese. This mutation causes an A to G change at nucleotide
position 493, producing an (165)Asn to Asp substitution. Interestingly, the
487 G----A and 493 A----G mutations create Alu I and Ava II recognition
sites, respectively, which enabled us to rapidly detect these two mutations
by PCR/restriction enzyme (RE) digestion method. The third mutation (1376
G----T) was found in four affected Chinese. This mutation causes a G to T
change at nucleotide position 1376 that results in an (459)Arg to Leu
substitution. The 1376 G----T mutation seems to be the dominant allele that
causes G6PD deficiency in Taiwan. Finally, two affected Chinese were
identified as having the fourth mutation (1388 G----A). This mutation
causes a G to A change at nucleotide 1388 that produces an (463)Arg to His
substitution. Our studies provide the direct proof of the genetic
heterogeneity of G6PD deficiency in the Chinese populations of Taiwan and
the PCR/RE digestion method is suitable for simultaneous detection of the
487 G----A and 493 A----G mutations.
Volume 79,
Issue 8,
pp. 2135-2140,
04/15/1992
Copyright © 1992 by The American Society of Hematology
