Hemophilia A is a heterogeneous hemorrhagic disorder caused by a large number of mutations. Recurrent mutations are rare, except intron 22 and intron 1 inversions. The substitution of a cytosine to a thymine at nucleotide 6046 in F8 gene was identified in a group of Italian patients affected by hemophilia A from a specific region of Northern Italy with a prevalence of 7.6%. This F8 variant was the second most frequent mutation in our cohort, after the intron 22 inversion. The identification of the same mutation in a restricted population gets to suppose the existence of a founder effect. Intragenic and extragenic polymorphic markers were tested to assess this assumption. A peculiar haplotype in linkage disequilibrium with this recurrent mutation (c.6046C>T) was identified in 71% of patients, supporting a founder effect. This distinctive haplotype was not identified in a control group (Fisher's exact test, P < 0.0001), coming from the same geographic region. These data strongly suggested the presence of a founder effect, supporting the existence of a single mutation event. Using DMLE+2.3 software and the mathematical approach described by Bengtsson and Thomson, the inferred age of this mutation is supposed to be about 2325 years (95% CI: 904-5081) ago.
A recurrent F8 mutation (c.6046C>T) causing hemophilia A in 8% of northern Italian patients : evidence for a founder effect / I. Garagiola, S. Seregni, M. Mortarino, M.E. Mancuso, M.R. Fasulo, L.D. Notarangelo, F. Peyvandi. - In: MOLECULAR GENETICS & GENOMIC MEDICINE. - ISSN 2324-9269. - 4:2(2016 Mar), pp. 152-159.
|Titolo:||A recurrent F8 mutation (c.6046C>T) causing hemophilia A in 8% of northern Italian patients : evidence for a founder effect|
GARAGIOLA, ISABELLA MARIA (Primo)
PAYVANDI, FLORA (Ultimo)
|Parole Chiave:||F8 gene; founder effect; haplotype analysis; hemophilia A; recurrent mutation|
|Settore Scientifico Disciplinare:||Settore MED/09 - Medicina Interna|
|Data di pubblicazione:||mar-2016|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1002/mgg3.189|
|Appare nelle tipologie:||01 - Articolo su periodico|
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