Title:Congenital FX Deficiency Rio Tercero: A New Heterozygous Missense Mutation (Cys241Gly) with a Potentiating Effect by a Polymorphism (c. 503-57C>T)#
Volume: 17
Issue: 2
Author(s): Antonio Girolami*, Salvador Minoldo, Silvia Ferrari, Diego Colussi, Anna Maria Lombardi and Hugo Guglielmone
Affiliation:
- Department of Medicine, University of Padua Medical School, Padua,Italy
Keywords:
FX deficiency, polymorphism, potentiating effect, new mutation, menorrhagia, plasma.
Abstract: Objective: The aim was to report a new family with congenital FX deficiency.
Patients and Methods: The proposita is a 41 year old female with a moderate bleeding tendency
(easy bruising, menorrhagia). Parents were not consanguineous. Family history was positive for a
mild bleeding tendency.
Results: Coagulation and genetics studies revealed that the proposita and two of her siblings were
heterozygotes for a new mutation Cys241Gly in exon 6 but had different FX level (2-3% of normal
in the proposita and about 50% in the two siblings. The same was true for one of her three children.
The mother and the other two children of the proposita had also slightly decreased FX levels but no
mutation. On the suspicion that the proposita was carrying another defect which had escaped the
Sanger method, we carried out a whole exome analysis and discovered that the proposita and one of
her siblings were also homozygous for a mutation of a known polymorphism (c.503-57C>T).
The daughter of the proposita was instead, besides being a carrier of the missense new mutation
Cys241Gly, heterozygous for the same polymorphism. The mother and two other daughters were
also heterozygous for the polymorphism. There were no deletions or duplications.
Conclusion: The polymorphism present in the family seems to be capable of potentiating the defect
induced by the new mutation. This, safe for epigenetics phenomena, is the only possible explanation
for the discrepancy found in the FX level between mother and daughter despite the fact that both
carried the same new mutation.
