In 1813 Hay1 described "a remarkable hemorrhagic disposition" in Oliver Appleton of Ipswich (Mass.), born in 1677, and in 18 of his male descendants. Hay recognized the pedigree pattern characteristic of a sex-linked recessive trait as well as the typical clinical features of hemophilia. In 1885 Osler2 obtained follow-up information adding 2 more affected males. The present investigation of the same family has had the following aspects:
Hemophilia has been traced back with reasonable certainty to the hemophilic maternal grandfather of Oliver Appleton, born in 1613.
Precise vital statistics and other information have been obtained for many of the family members referred to by Hay and Osler.
The kindred has been traced to the present in as complete detail as possible with demonstration of a total of 25 hemophilic males and 27 carrier females and with identification of the gene in one presently living descendant.