[Prenatal diagnosis of glycogen storage disease Ia by screening for hot spot mutations in combination with the 1176 nucleotide polymorphism linkage analysis].
OBJECTIVE
To develop and evaluate a simple, fast and accurate prenatal diagnosis method for glycogen storage disease Ia (GSD Ia) in Chinese.


METHODS
This study involved 3 unrelated families. Genomic DNA samples were extracted from the blood of three GSD Ia patients and their parents, from the amniocytes of 3 fetuses and the blood of 2 newborns. By the way of restriction enzyme analysis, the screening for 727G-->T and R83H mutations of glucose-6-phosphatase gene was carried out in conjunction with 1176 nucleotide polymorphism linkage analysis so as to make the gene and prenatal diagnosis of 3 GSD Ia families. Direct DNA sequencing of the corresponding PCR products was used to confirm the unveiled mutations and 1176 nucleotide polymorphism.


RESULTS
Three probands were homozygotes for the 727G-->T mutation and their parents were heterozygotes for this mutation. The fetuses of family 1 and 3 were heterozygotes for the 727G-->T mutation, whereas the fetus of family 2 did not carry this mutation. The 1176 nucleotide polymorphisms of 3 fetuses were different from those of the corresponding probands. The prenatal diagnoses of family 1 and 2 were confirmed by the postnatal biochemical and molecular studies.


CONCLUSIONS
These findings suggest that the screening for 727G-->T and R83H mutations in conjunction with the 1176 polymorphism linkage analysis be a simple, fast and accurate method for gene and prenatal diagnosis of GSD Ia in Chinese.
Qiu
Wen-juan
WJ
Department of Pediatric Endocrinology and Genetic Metabolism, Xinhua Hospital Affiliated to Shanghai Second Medical University, Shanghai Institute for Pediatric Research, Shanghai, 200092 PR China. wenjuan_qiu @sina.com
Zhang
Ya-fen
YF
Pan
Jun
J
Ye
Jun
J
Liu
Xiao-qing
XQ
Han
Lian-shu
LS
Gu
Xue-fan
XF
D000328:Adult; D002648:Child; D002675:Child, Preschool; D005192:Family Health; D005260:Female; D008040:Genetic Linkage; D005952:Glucose-6-Phosphatase / Q000235:genetics; D005953:Glycogen Storage Disease Type I / Q000175:diagnosis* / Q000235:genetics*; D006801:Humans; D008297:Male; D010375:Pedigree; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods*
D005952:Glucose-6-Phosphatase