title: A cluster of factor XI-deficient patients due to a new mutation (Ile 436 Lys) in northeastern Italy.
abstract: A new mutation (Ile 436 Lys) was found in a cluster of patients in northeastern Italy. The mutation was present in five patients at the homozygote level and in one patient as a compound heterozygote with an already known mutation namely Glu 117 stop. All these patients showed a mild bleeding tendency mainly associated with deliveries or surgery. The first two patients were two sisters, and their parents were consanguineous. The third patient was the only homozygote in the family, and parents apparently were not consanguineous. The fourth and fifth patients were a brother and a sister, and in this case too, parents were not consanguineous. The sixth patient, a compound heterozygote, negated also the existence of consanguinity between his parents. There were also seven heterozygotes among the family members of the patients homozygous for this new mutation (Ile 436 Lys). Finally, there were two heterozygotes for the Glu 117 stop mutation in the family of the sixth patient. The heterozygotes, regardless of the mutation, were asymptomatic. The Ile436Lys mutation is characterized by low factor XI activity and antigen, namely is a cross-reaction material negative form. Molecular modeling indicates that the Ile436Lys mutation causes a large conformational change within the 432-442 loop. No relation could be traced among the different families; however, all their ancestors were autochthonous of the same two small towns. Furthermore, no Jewish ancestry could be found. The close geographical area in which all these patients were found and the absence of the same mutation in the general population of the area strongly suggests a founder effect and that the mutation is responsible for the defect. The compound heterozygosis with the Glu 117 stop mutation, common among Jews, was not surprising because of the past strict ties of the Republic of Venice with the Middle East.
authors: Department of Medical and Surgical Sciences, University of Padua Medical School, Padua, Italy. antonio.girolami@unipd.it
authors: Antonio
authors: A
authors: Girolami
authors: Pamela
authors: P
authors: Scarparo
authors: Emanuela
authors: E
authors: Bonamigo
authors: Liliana
authors: L
authors: Santarossa
authors: Andrea
authors: A
authors: Cristiani
authors: Stefano
authors: S
authors: Moro
authors: Anna Maria
authors: AM
authors: Lombardi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution; D001483:Base Sequence; D003241:Consanguinity; D005172:Factor XI / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D005173:Factor XI Deficiency / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005838:Genotype; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D011487:Protein Conformation; D055815:Young Adult
chemical_list: D005172:Factor XI