Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2009-1-15
pubmed:abstractText
Haemophilia A (HA) is an X-linked recessive haemorrhagic disorder caused by a deficiency of coagulation factor VIII. Disease causative mutations are heterogeneous and spread all over the F8 gene sequence, with the exception of intron 22 inversion occurring in about 50% of severe patients. To define the specific mutational repertoire and mutation detection rate, we analysed F8 gene, by polymerase chain reaction and direct sequencing, in 128 unrelated patients from Southern Italy with severe (n = 108), moderate (n = 9) or mild (n = 11) HA. We identified 120 mutations, including 64 cases of intron 22 inversion (53.3%), three of intron 1 inversion (2.5%), one large deletion (0,8%) and 52 point mutations (43.3%). In particular, 19/120 were novel and 7/52 point mutations (13.5%) occurred at CpG sites. We also investigated eight prothrombotic genetic variants in a subgroup of 74 severe HA patients to evaluate their possible protective effect on the severity of clinical expression. Methylenetetrahydrofolate reductase A1298C and plasminogen activator inhibitor-1 4G variants recurred more frequently in HA patients with a less-severe phenotype. Clinical impact of these findings needs large-scale studies to further define the role of these prothrombotic variants as possible modifier factors of HA phenotype.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1365-2516
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
14
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
796-803
pubmed:dateRevised
2009-10-21
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Mutational spectrum of F8 gene and prothrombotic gene variants in haemophilia A patients from Southern Italy.
pubmed:affiliation
Dipartimento di Biochimica e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, CEINGE- Biotecnologie Avanzate, Via Comunale Margherita n. 482, Naples, Italy.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't