Origin of Swedish hemophilia B mutations.
BACKGROUND
More than 1100 mutations that cause hemophilia B (HB) have been identified. At the same time, specific F9 mutations are present at high frequencies in certain populations, which raise questions about the origin of HB mutations.


OBJECTIVE
To describe the mutation spectrum of all HB families in Sweden and investigate if mutations appearing in several families are due to independent recurrent mutations (RMs) or to a common mutation event (i.e. are identical by descent (IBD)).


METHODS
The registered Swedish HB population consists of patients from 86 families. Mutations were identified by resequencing and identical haplotypes were defined using 74 markers and a control population of 285 individuals. The ages of IBD mutations were estimated using ESTIAGE.


RESULTS
Out of 77 presumably unrelated patients with substitution mutations, 47 patients (61%) had mutations in common with other patients. Haplotyping of the 47 patients showed that 24 patients had IBD mutations (51%) with estimated ages of between two and 23 generations. A majority of these patients had mild disease. Eight of the 15 mutations observed in more than one family were C>T transitions in CpG sites and all eight were RMs.


CONCLUSIONS
The association of IBD mutations with a mild phenotype is similar to what has been previously observed in hemophilia A. Noteworthy features of the mutations that are common to more than one family are the equal proportions of patients with RM and IBD mutations and the correlation between the occurrence of RMs and C>T transitions at CpG sites.
Biomedicine, Kristianstad University, Kristianstad, Sweden.
C
C
Halldén
A
A
Mårtensson
D
D
Nilsson
T
T
Säll
C
C
Lind-Halldén
A C
AC
Lidén
R
R
Ljung
D018899:CpG Islands; D004252:DNA Mutational Analysis; D005164:Factor IX / Q000235:genetics*; D018703:Founder Effect; D017353:Gene Deletion; D005819:Genetic Markers; D005838:Genotype; D006239:Haplotypes; D002836:Hemophilia B / Q000235:genetics*; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D009154:Mutation; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012042:Registries; D013548:Sweden
D005819:Genetic Markers; D005164:Factor IX
factor IX; founder effect; haplotypes; hemophilia B; mutation