The Molecular Basis of Severe Hemophilia B in a Girl

Severe phenotypic expression of recessive X-linked disorders in females is rare, although examples have been reported. Cases have been documented in females who were homozygous for a recessive allele¹ and in female patients with Turner's syndrome² or a structural abnormality of the X chromosome.^{3 4 5} In females with apparently normal X chromosomes, “extreme lyonization” (that is, deviation from random X-chromosome inactivation) has been postulated to be the cause of severe clinical expression of X-linked recessive disorders.^6,7 Nonrandom inactivation has been documented in females with structural X-chromosome abnormalities such as deletions^8,9; inactivation of the abnormal X chromosome tends to minimize the.