title: Large deletions play a minor but essential role in congenital coagulation factor VII and X deficiencies.
abstract: Congenital factor VII (FVII) and factor X (FX) deficiencies belong to the group of rare bleeding disorders which may occur in separate or combined forms since both the F7 and F10 genes are located in close proximity on the distal long arm of chromosome 13 (13q34). We here present data of 192 consecutive index cases with FVII and/or FX deficiency. 10 novel and 53 recurrent sequence alterations were identified in the F7 gene and 5 novel as well as 11 recurrent in the F10 gene including one homozygous 4.35 kb deletion within F7 (c.64+430_131-6delinsTCGTAA) and three large heterozygous deletions involving both the F7 and F10 genes. One of the latter proved to be cytogenetically visible as a chromosome 13q34 deletion and associated with agenesis of the corpus callosum and psychomotor retardation.
  
  
  CONCLUSIONS
  Large deletions play a minor but essential role in the mutational spectrum of the F7 and F10 genes. Copy number analyses (e. g. MLPA) should be considered if sequencing cannot clarify the underlying reason of an observed coagulopathy. Of note, in cases of combined FVII/FX deficiency, a deletion of the two contiguous genes might be part of a larger chromosomal rearrangement.
authors.forename: M
authors.initials: M
authors.lastname: Rath
authors.forename: J
authors.initials: J
authors.lastname: Najm
authors.forename: H
authors.initials: H
authors.lastname: Sirb
authors.forename: K
authors.initials: K
authors.lastname: Kentouche
authors.forename: A
authors.initials: A
authors.lastname: Dufke
authors.forename: S
authors.initials: S
authors.lastname: Pauli
authors.forename: K
authors.initials: K
authors.lastname: Hackmann
authors.forename: T
authors.initials: T
authors.lastname: Liehr
authors.forename: C A
authors.initials: CA
authors.lastname: Hübner
authors.affiliation: Prof. Dr. med. Ute Felbor, Department of Human Genetics, University Medicine Greifswald, Fleischmannstr. 42-44, 17475 Greifswald, Germany, Tel. +49/(0)38 34/86 53 71, Fax +49/(0)38 34/86 53 69, felbor@uni-greifswald.de.
authors.forename: U
authors.initials: U
authors.lastname: Felbor
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D005167:Factor VII / Q000235:genetics*; D005168:Factor VII Deficiency / Q000151:congenital / Q000453:epidemiology* / Q000235:genetics*; D005170:Factor X / Q000235:genetics*; D005171:Factor X Deficiency / Q000151:congenital / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D005858:Germany / Q000453:epidemiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D012307:Risk Factors; D055815:Young Adult
chemical_list: D005167:Factor VII; D005170:Factor X
keywords: F10 gene; F7 gene; Factor VII deficiency; chromosome 13q34 deletion; factor X deficiency