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Article: Gene mutations in 21 unrelated cases of phenotypic heterozygous protein C deficiency and thrombosis

TitleGene mutations in 21 unrelated cases of phenotypic heterozygous protein C deficiency and thrombosis
Authors
Issue Date1996
PublisherSchattauer GmbH. The Journal's web site is located at http://www.thrombosis-online.com
Citation
Thrombosis And Haemostasis, 1996, v. 76 n. 6, p. 867-873 How to Cite?
AbstractMutations have been identified in the protein C gene in 21 patients with venous thromboembolism and phenotypic heterozygous protein C deficiency. In 20 probands, single mutations were the only abnormalities identified by sequencing all coding regions, intron exon boundaries and the promoter region back to -1540. In one proband 2 mutations were identified and in another family 2 mutations were identified (but not both in the proband). Of the 23 mutations, 18 resulted in predicted amino acid substitutions, 3 were mutations resulting in stop codons, one was a mutation within a consensus splice sequence and another a 9 base pair insertion within exon 5 (this region within exon 5 is proposed as a deletion/insertion hot spot). A novel polymorphism was also, uniquely, identified in the propeptide region of the molecule (Pro-21Pro; CCT to CCC) in a kindred from Hong Kong. Cosegregation of the protein C gene mutation with protein C deficiency could be determined in 13 families. In a further family, phenotypic protein C deficiency and the genetic mutation cosegregated in only 4/5 members, The first thrombotic incident occurred in the probands between the ages of 11 and 59 years and 12 individuals suffered recurrent thrombosis. Thrombosis occurred in at least one other family member in 9/21 families, but in 2 of these it was inconsistently associated with protein C deficiency. An independent genetic risk factor, factor V Arg506Gln (FV Leiden) was identified in 2 probands (and 3 family members) and in 4 protein C deficient members of a third family but not in the proband. The results suggest that in the majority of probands with thrombosis and phenotypic protein C deficiency, a single protein C gene mutation is associated with thrombosis. However, it is also possible that additional unknown genetic risk factors contribute to the thrombotic risk. An added, acquired, risk factor leads to thrombosis at an early age (< 25 years).
Persistent Identifierhttp://hdl.handle.net/10722/57150
ISSN
2015 Impact Factor: 5.255
2015 SCImago Journal Rankings: 2.089
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorIreland, Hen_HK
dc.contributor.authorThompson, Een_HK
dc.contributor.authorLane, DAen_HK
dc.contributor.authorChan, LCen_HK
dc.contributor.authorConard, Jen_HK
dc.contributor.authorDe Caterina, Men_HK
dc.contributor.authorRocco, Ven_HK
dc.contributor.authorDe Stefano, Ven_HK
dc.contributor.authorLeone, Gen_HK
dc.contributor.authorFinazzi, Gen_HK
dc.contributor.authorHalil, Oen_HK
dc.contributor.authorLaffan, Men_HK
dc.contributor.authorMachin, Sen_HK
dc.contributor.authorWoodcock, Ben_HK
dc.date.accessioned2010-04-12T01:27:23Z-
dc.date.available2010-04-12T01:27:23Z-
dc.date.issued1996en_HK
dc.identifier.citationThrombosis And Haemostasis, 1996, v. 76 n. 6, p. 867-873en_HK
dc.identifier.issn0340-6245en_HK
dc.identifier.urihttp://hdl.handle.net/10722/57150-
dc.description.abstractMutations have been identified in the protein C gene in 21 patients with venous thromboembolism and phenotypic heterozygous protein C deficiency. In 20 probands, single mutations were the only abnormalities identified by sequencing all coding regions, intron exon boundaries and the promoter region back to -1540. In one proband 2 mutations were identified and in another family 2 mutations were identified (but not both in the proband). Of the 23 mutations, 18 resulted in predicted amino acid substitutions, 3 were mutations resulting in stop codons, one was a mutation within a consensus splice sequence and another a 9 base pair insertion within exon 5 (this region within exon 5 is proposed as a deletion/insertion hot spot). A novel polymorphism was also, uniquely, identified in the propeptide region of the molecule (Pro-21Pro; CCT to CCC) in a kindred from Hong Kong. Cosegregation of the protein C gene mutation with protein C deficiency could be determined in 13 families. In a further family, phenotypic protein C deficiency and the genetic mutation cosegregated in only 4/5 members, The first thrombotic incident occurred in the probands between the ages of 11 and 59 years and 12 individuals suffered recurrent thrombosis. Thrombosis occurred in at least one other family member in 9/21 families, but in 2 of these it was inconsistently associated with protein C deficiency. An independent genetic risk factor, factor V Arg506Gln (FV Leiden) was identified in 2 probands (and 3 family members) and in 4 protein C deficient members of a third family but not in the proband. The results suggest that in the majority of probands with thrombosis and phenotypic protein C deficiency, a single protein C gene mutation is associated with thrombosis. However, it is also possible that additional unknown genetic risk factors contribute to the thrombotic risk. An added, acquired, risk factor leads to thrombosis at an early age (< 25 years).en_HK
dc.languageengen_HK
dc.publisherSchattauer GmbH. The Journal's web site is located at http://www.thrombosis-online.comen_HK
dc.relation.ispartofThrombosis and Haemostasisen_HK
dc.rightsThrombosis and Haemostasis. Copyright © Schattauer GmbH.en_HK
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.rightsThis article is not an exact copy of the original published article in Thrombosis and Haemostasis. The definitive publisher-authenticated version of Thrombosis and Haemostasis, 1996, v. 76 n. 6, p. 867-873is available online at: http://www.thrombosis-online.comen_HK
dc.subject.meshProtein C Deficiencyen_HK
dc.subject.meshThrombosis - geneticsen_HK
dc.subject.meshMolecular Sequence Dataen_HK
dc.subject.meshPolymorphism, Geneticen_HK
dc.subject.meshProtein C - geneticsen_HK
dc.titleGene mutations in 21 unrelated cases of phenotypic heterozygous protein C deficiency and thrombosisen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0340-6245&volume=76&issue=6&spage=867&epage=873&date=1996&atitle=Gene+mutations+in+21+unrelated+cases+of+phenotypic+heterozygous+Protein+C+deficiency+and+thrombosisen_HK
dc.identifier.emailChan, LC:chanlc@hkucc.hku.hken_HK
dc.identifier.authorityChan, LC=rp00373en_HK
dc.description.naturepublished_or_final_versionen_HK
dc.identifier.pmid8972002-
dc.identifier.scopuseid_2-s2.0-8044234364en_HK
dc.identifier.hkuros26171-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-8044234364&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume76en_HK
dc.identifier.issue6en_HK
dc.identifier.spage867en_HK
dc.identifier.epage873en_HK
dc.identifier.isiWOS:A1996VZ47800006-
dc.publisher.placeGermanyen_HK

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