Common mutations in the phosphofructokinase-M gene in Ashkenazi Jewish patients with glycogenesis VII - and their population frequency

Journal Article · Mon Aug 01 04:00:00 EDT 1994 · American Journal of Human Genetics; (United States)

OSTI ID:6949922

Sherman, J B; Raben, N; Nicastri, C; Adams, E M; Plotz, P H ^[1]; Argov, Z ^[2]; Nakajima, Hiromu ^[3]; Eng, C M; Cowan, T M ^[4]

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1. National Institutes of Health, Bethesda, MD (United States)
2. Hebrew Univ., Jerusalem (Israel)
3. Osaka Univ. (Japan)
4. Univ. of Maryland School of Medicine, Baltimore, MD (United States)

Phosphofructokinase (PFK) catalyzes the rate-limiting step of glycolysis. Deficiency of the muscle enzyme is manifested by exercise intolerance and a compensated hemolytic anemia. Case reports of this autosomal recessive disease suggest a predominance in Ashkenazi Jews in the United States. The authors have explored the genetic basis for this illness in nine affected families and surveyed the normal Ashkenazi population for the mutations found. Genomic DNA was amplified using PCR, and denaturing gradient-gel electrophoresis. The polymorphic exons were sequenced or digested with restriction enzymes. A previously described splicing mutation, [Delta]5, accounted for 11 (61%) of 18 abnormal alleles in the nine families. A single base deletion leading to a frameshift mutation in exon 22 ([Delta]C-22) was found in six of seven alleles. A third mutation, resulting in a nonconservative amino acid substitution in exon 4, accounted for the remaining allele. Thus, three mutations could account for an illness in this group, and two mutations could account for 17 of 18 alleles. In screening 250 normal Ashkenazi individuals for all three mutations, they found only one [Delta]5 allele. Clinical data revealed no correlation between the particular mutations and symptoms, but male patients were more symptomatic than females, and only males had frank hemolysis and hyperuricemia. Because PFK deficiency in Ashkenazi Jews is caused by a limited number of mutations, screening genomic DNA from peripheral blood for the described mutations in this population should enable rapid diagnosis without muscle biopsy. 41 refs., 4 figs., 2 tabs.

• OSTI ID: 6949922
• Journal Information: American Journal of Human Genetics; (United States), Journal Name: American Journal of Human Genetics; (United States) Vol. 55:2; ISSN AJHGAG; ISSN 0002-9297
• Country of Publication: United States
• Language: English

Related Subjects

550400* -- Genetics
59 BASIC BIOLOGICAL SCIENCES
CARBOHYDRATES
DNA SEQUENCING
ENZYMES
FRUCTOSE
GENE MUTATIONS
HEXOSES
KETONES
METABOLISM
MONOSACCHARIDES
MUTATIONS
ORGANIC COMPOUNDS
PHOSPHORUS-GROUP TRANSFERASES
PHOSPHOTRANSFERASES
PROTEINS
SACCHARIDES
STRUCTURAL CHEMICAL ANALYSIS
TRANSFERASES