Female monozygotic twins discordant for hemophilia A due to nonrandom X-chromosome inactivation

Abstract

We describe monozygotic female twins discordant for hemophilia A, born to a carrier mother and normal father. Affected twin A presented at age 1 year with excessive bruising and factor VIII procoagulant activity (FVIII:C) of less than 1% of normal. Twin B is an asymptomatic carrier with FVIII:C level of 42%. Peripheral blood DNA was tested for X-chromosome inactivation (methylation) patterns of the X-linked human androgen receptor gene, comparing the twins' patterns to parental. Twin A showed nonrandom inactivation skewed toward the paternal X, whereas twin B showed random X-inactivation. This is the first reported case of discordance for hemophilia A between female monozygotic twins. © 2008 Wiley-Liss, Inc.