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S Gandrille and M Aiach
INSERM U 428, Unite de Formation et de Recherche (UFR) des Sciences
Pharmaceutiques et Biologiques, Paris, France.
By studying the protein C gene of 121 consecutive patients with symptomatic
type I protein C deficiency, we detected 55 different candidate mutations
in 90 cases. The mutations, 76% of which were missense changes, were
distributed throughout the gene. More than half the missense mutations
involved Cys, Phe, Pro, or Gly, amino acids known to affect the structure
of the polypeptide chain by various mechanisms. Thus, 40% of protein C
deficiencies may be caused by polypeptide chain instability rather than a
lack of expression of the mutated allele; this may also account for
phenotypic heterogeneity. Seventeen of the 55 different mutations were
found in apparently unrelated families. Half the French families we studied
bore one of these 17 mutations. The wide variety of mutations suggests that
both sporadic cases and a founder effect contribute to the spectrum of
protein C mutations in a given population. The differences in both unique
and recurrent mutations in French and Dutch populations-the only large
population samples so far studied-support this hypothesis.
This article has been cited by other articles:
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| Copyright © 1995 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||
