Document Detail


The problem of novel FVIII missense mutations for haemophilia A genetic counseling.
MedLine Citation:
PMID:  19404520     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Molecular genetic testing for factor VIII (FVIII) mutations is indicated in haemophilia A since determination of FVIII activity cannot reliably identify female carriers. Given the large number of FVIII mutations the identification of novel mutations is not uncommon. Since amino acid polymorphisms of FVIII are rare, missense mutations in patients with haemophilia A which are not found in the normal population are considered as causative in general practice when no other mutation can be detected by complete FVIII gene sequencing. We report a novel rare missense variant (P2311S) in a haemophilia A family that was mistakenly considered as pathogenic leading to amniocentesis, prenatal diagnosis and influenced the peripartal management of the putatively affected child. Subsequently, we identified the novel causative mutation V197G in the family's index case which could be detected neither in the neonate nor in his mother. CONCLUSION: This case emphasizes the necessity to establish the molecular diagnosis in the family's index case and to perform expression studies of novel mutations to prove their causative nature.
Authors:
Reinhard Schneppenheim; J Schröder; T Obser; F Oyen; S Schneppenheim; J Oldenburg
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Hämostaseologie     Volume:  29     ISSN:  0720-9355     ISO Abbreviation:  Hamostaseologie     Publication Date:  2009 May 
Date Detail:
Created Date:  2009-04-30     Completed Date:  2009-07-07     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8204531     Medline TA:  Hamostaseologie     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  158-60     Citation Subset:  IM    
Affiliation:
Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany. schneppenheim@uke.de
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MeSH Terms
Descriptor/Qualifier:
Factor VIII / genetics*
Female
Genetic Counseling*
Genetic Vectors
Hemophilia A / genetics*
Humans
Male
Mutation, Missense*
Pedigree
Sequence Deletion
Chemical
Reg. No./Substance:
9001-27-8/Factor VIII

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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