First de novo mutations in the protein C gene of two patients with type I
deficiency: a missense mutation and a splice site deletion
S Gandrille, B Jude, M Alhenc-Gelas, J Emmerich and M Aiach
INSERM CJF 91-01, UFR des Sciences Pharmaceutiques et Biologiques,
Universite Rene Descartes, Paris, France.
In a series of 40 patients with symptomatic protein C deficiency, we
identified two sporadic cases with novel mutations that probably affect
gene expression. The mutations, a 5-bp deletion of the donor splice site of
intron f (nucleotides 3455 to 3459) and a mutation of nucleotide 8523 in
exon IX leading to the substitution of Ser 270 by Pro, were not found in
the protein C gene of the patients' parents. Transmission of the paternal
and maternal protein C alleles was apparently normal on the basis of
frequent polymorphisms in exons I, VI, and VIII. We also checked the
transmission of the chromosomal material by analyzing the beta-globin gene
frameworks and three variable number of tandem repeats (VNTRs). By
combining the results of intragenic polymorphism, VNTR and beta-globin gene
framework analyses, we were able to exclude nonpaternity and confirm the de
novo origin of the mutation.
Volume 84,
Issue 8,
pp. 2566-2570,
10/15/1994
Copyright © 1994 by The American Society of Hematology
