Severe FVII deficiency caused by a new point mutation combined with a previously undetected gene deletion.

Summary A 3-week-old Caucasian female presented with severe unprovoked parenchymal cerebral haemorrhage. Her plasma factor VII (FVII) activity was  A) changing the codon for Glu29 to Lys (E29K); neither parent had the E29K mutation. Because of the unlikelihood that the proband was homozygous for two identical new point mutations, the DNA sequence abnormality was more likely to have arisen from a single mutated gene on one allele and a F7 gene deletion on the other allele. Real time polymerase chain reaction (PCR) analysis confirmed that the proband had inherited a gene deletion that was present in the maternal side of the family. Subsequent clotting assays and real time PCR revealed that the maternal deletion also included the closely linked F10 gene.