Female monozygotic twins discordant for hemophilia A due to nonrandom X-chromosome inactivation.
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.
Bennett
Carolyn M
CM
Division of Hematology/Oncology, Children's Hospital Boston, Boston, Massachusetts 02115, USA.
Boye
Eileen
E
Neufeld
Ellis J
EJ
D004252:DNA Mutational Analysis; D004200:Diseases in Twins / Q000235:genetics*; D004303:Dosage Compensation, Genetic; D005169:Factor VIII / Q000235:genetics; D005260:Female; D008040:Genetic Linkage; D005819:Genetic Markers; D006467:Hemophilia A / Q000235:genetics*; D006801:Humans; D009154:Mutation; D010375:Pedigree; D014430:Twins, Monozygotic / Q000235:genetics*; D049951:X Chromosome Inactivation
D005819:Genetic Markers; D005169:Factor VIII