TY - JOUR
T1 - Recurrent mutations in haemophilia a give evidence for CpG mutation hotspots
AU - Youssoufian, Hagop
AU - Kazazian, Haig H.
AU - Phillips, Deborah G.
AU - Aronis, Sophia
AU - Tsiftis, George
AU - Brown, Valerie A.
AU - Antonarakis, Stylianos E.
PY - 1986
Y1 - 1986
N2 - Haemophilia A is a common disorder of blood coagulation caused by a deficiency of factor VIII1. It is inherited as an X-linked recessive trait, and one-third of all cases are thought to result from de novo mutations2. The clinical severity of haemophilia A varies markedly among different families and a subset of the patients with severe disease develop antibodies against factor VIII, called inhibitors3. Because of this heterogeneity, it is likely that many different molecular lesions result in haemophilia A. Indeed, of the nine mutations described to date, all appear to be unique changes4-6. However in this study of 83 patients with haemophilia A we have identified two different point mutations, one in exon 18 and one in exon 22, that have recurred independently in unrelated families. Each mutation produces a nonsense codon by a change of CG to TG, and each occurred de novo on the X-chromosome donated by the maternal grandfather. These observations strongly support the view that CpG dinucleotides are mutation hotspots.
AB - Haemophilia A is a common disorder of blood coagulation caused by a deficiency of factor VIII1. It is inherited as an X-linked recessive trait, and one-third of all cases are thought to result from de novo mutations2. The clinical severity of haemophilia A varies markedly among different families and a subset of the patients with severe disease develop antibodies against factor VIII, called inhibitors3. Because of this heterogeneity, it is likely that many different molecular lesions result in haemophilia A. Indeed, of the nine mutations described to date, all appear to be unique changes4-6. However in this study of 83 patients with haemophilia A we have identified two different point mutations, one in exon 18 and one in exon 22, that have recurred independently in unrelated families. Each mutation produces a nonsense codon by a change of CG to TG, and each occurred de novo on the X-chromosome donated by the maternal grandfather. These observations strongly support the view that CpG dinucleotides are mutation hotspots.
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U2 - 10.1038/324380a0
DO - 10.1038/324380a0
M3 - Article
C2 - 3097553
AN - SCOPUS:0022967463
SN - 0028-0836
VL - 324
SP - 380
EP - 382
JO - Nature
JF - Nature
IS - 6095
ER -