FAMILY STUDIES IN AN EXTREMELY LARGE MILD HEMOPHILIA-A PEDIGREE WHICH INCLUDES 10-PERCENT OF GREEK HEMOPHILIACS

We illustrate the usefulness of direct mutation detection for genetic counselling by showing its application to an extremely large mild haemophilia A pedigree (91 haemophiliacs) originating from the village of Aiani in Macedonia, northern Greece. The causative mutation has already been shown to be an A to T transversion in codon 280 of the FVIII gene which replaces Asn 280 (AAC) by Ile (ATC) and which creates a new Bam HI restriction site in, exon 7. The latter permitted direct, rapid and reliable detection of the mutation in relevant family members, All major branches of the family were shown to share the mutation, and carrier status was diagnosed or excluded for 23 possible carriers. Other interesting characteristics of the Aiani haemophilic population are a slightly higher longevity and fecundity than that observed in the general population and a wide range of FVIII:C levels (5-25%) associated with the mutation.