Document Detail

Intron 22 homologous regions are implicated in exons 1-22 duplications of the F8 gene.
MedLine Citation:
PMID:  23299923     Owner:  NLM     Status:  MEDLINE    
The intron 22 inversion found in up to 50% of severe hemophilia A patients results from a recombination between three intron 22 homologous copies (int22h). This study evaluated the implication of these copies in the formation of extended duplications comprising exons 1-22 of the factor 8 (F8) gene and their association with hemophilia and mental retardation. Two hemophilic patients with moderate and severe phenotypes and a third nonhemophilic patient with developmental delay were studied. All exhibited a duplication of F8 gene exons 1-22 identified by multiplex ligation-dependent probe amplification along with abnormal patterns on Southern blotting and unexpected long-range PCR amplification. Breakpoint analysis using array comparative genomic hybridization was performed to delimit the extent of these rearrangements. These duplications were bounded on one side by the F8 intragenic int22h-1 repeat and on the other side by extragenic int22h-2 or int22h-3 copies. However, the simultaneous identification of a second duplication containing F8 gene exons 2-14 for the moderate patient and the classical intron 22 inversion for the severe patient are considered in this study as the genetic causal defects of hemophilia. This study shows that the well-known int22h copies are involved in extended duplications comprising F8 gene exons 1-22. These specific duplications are probably not responsible for hemophilia and intellectual disability, but should be carefully considered in genetic counseling, while continuing to investigate the causal mutation of hemophilia.
Nathalie Lannoy; Bernard Grisart; Stéphane Eeckhoudt; Christine Verellen-Dumoulin; Catherine Lambert; Miikka Vikkula; Cédric Hermans
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2013-01-09
Journal Detail:
Title:  European journal of human genetics : EJHG     Volume:  21     ISSN:  1476-5438     ISO Abbreviation:  Eur. J. Hum. Genet.     Publication Date:  2013 Sep 
Date Detail:
Created Date:  2013-08-16     Completed Date:  2014-03-24     Revised Date:  2014-09-02    
Medline Journal Info:
Nlm Unique ID:  9302235     Medline TA:  Eur J Hum Genet     Country:  England    
Other Details:
Languages:  eng     Pagination:  970-6     Citation Subset:  IM    
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MeSH Terms
Child, Preschool
Comparative Genomic Hybridization
DNA Mutational Analysis
Factor VIII / genetics*
Genetic Association Studies
Hemophilia A / genetics*
Intellectual Disability / genetics*
Segmental Duplications, Genomic
Sequence Homology, Nucleic Acid
Reg. No./Substance:
0/F8 protein, human; 9001-27-8/Factor VIII

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

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