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Mutations in muscle phosphofructokinase gene
1Arthritis and Rheumatism Branch, National Institute of Arthritis, Musculoskeletal, and Skin Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Abstract:
Mutations in the muscle phosphofructokinase gene (PFK-M) result in a metabolic myopathy characterized by exercise intolerance and compensated hemolysis. PFK deficiency, glycogenosis type VII (Tarui disease) is a rare, autosomal, recessively inherited disorder. Multiple mutations, including splicing defects, frameshifts, and missense mutations, have recently been identified in patients from six different ethnic backgrounds establishing genetic heterogeneity of the disease. There is no obvious correlation between the genotype and phenotypic expression of the disease. PFK-M deficiency appears to be prevalent among people of Ashkenazi Jewish descent. Molecular diagnosis is now feasible for Ashkenazi patients who share two common mutations in the gene; the more frequent is an exon 5 splicing defect, which accounts for approximately 68% of mutant alleles in this population.
Insights
Muscle phosphofructokinase (PFK) deficiency, or Tarui disease, causes exercise intolerance. Two common mutations in Ashkenazi Jewish populations facilitate molecular diagnosis.
Area of Science:
- Biochemistry
- Genetics
- Metabolic Disorders
Background:
- Muscle phosphofructokinase (PFK-M) gene mutations cause a metabolic myopathy, leading to exercise intolerance and compensated hemolysis.
- PFK deficiency, also known as glycogenosis type VII or Tarui disease, is a rare autosomal recessive disorder.
- Genetic heterogeneity is established, with multiple mutation types identified across diverse ethnic groups.
Purpose of the Study:
- To investigate the genetic basis and ethnic prevalence of PFK-M deficiency.
- To explore the feasibility of molecular diagnosis for specific populations.
Main Methods:
- Identification of various mutations (splicing defects, frameshifts, missense) in the PFK-M gene.
- Analysis of genotype-phenotype correlations.
- Prevalence assessment in different ethnic groups, particularly Ashkenazi Jewish descent.
Main Results:
- No clear correlation was found between genotype and the clinical presentation of Tarui disease.
- PFK-M deficiency shows higher prevalence in individuals of Ashkenazi Jewish descent.
- Two common PFK-M mutations are identifiable in Ashkenazi patients, enabling molecular diagnosis.
Conclusions:
- Molecular diagnosis for Tarui disease is feasible, especially in the Ashkenazi Jewish population, due to shared mutations.
- An exon 5 splicing defect is the most frequent mutation (approx. 68%) among Ashkenazi alleles.
- Further research into the genetic heterogeneity and ethnic-specific prevalence of PFK-M deficiency is warranted.