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Mutation analysis impact on the genetic counseling of sporadic hemophilia B families
Author(s) -
Bicocchi Maria Patrizia,
Pasino Mirella,
Bottini Federico,
Lanza Tiziana,
Mori Pier Giorgio,
Acquila Maura
Publication year - 2003
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.20016
Subject(s) - pedigree chart , genetics , mutation , genetic counseling , restriction fragment length polymorphism , factor ix , gene , heteroduplex , prenatal diagnosis , biology , genetic analysis , mutation testing , microbiology and biotechnology , polymerase chain reaction , pregnancy , fetus
Previous studies have shown that hemophilia B (HB) is the result of several different mutations, mostly single nucleotide substitutions, in the factor IX ( FIX ) gene. In order to evaluate the impact of mutation analysis on genetic counseling in sporadic and uninformative HB familial pedigrees, we re‐analyzed by the conformation sensitive gel electrophoresis (CSGE) technique 14 patients, previously studied by restriction fragment length polymorphisms (RFLPs). A single mutation was present within the FIX gene of each patient: 12 mutations were single base substitutions, 1 was a base insertion, and 1 was a four nucleotide deletion; 4/12 mutations have not been described so far. By identifying the detrimental mutations in affected males, carrier status was correctly diagnosed in all the women we studied; 3/12 de novo events were found in maternal meioses with a 25% mutation rate. Identification of the genetic defect was also successfully applied to three prenatal diagnoses. © 2003 Wiley‐Liss, Inc.