A de novo translocation 46,X,t(X;15) causing haemophilia B in a girl: a case report

Abstract

Haemophilia B is an X-linked recessive bleeding disorder caused by mutations in the factor IX gene with an incidence of 1:25000-30000. Usually female carriers are clinically normal, and severe phenotypic expression of the disease in females is extremely rare. In this report we describe a girl with a clinically severe course of haemophilia B who had no signs of Turner syndrome or any other dysmorphic features. Cytogenetic and molecular studies in the patient and her parents showed a de novo translocation 46,X,t(X;15)(q27.1;p11.2) in the patient, indicating a possible break near the factor IX gene. The structurally normal X chromosome was late replicating and inactivated in all metaphases as shown by high-resolution R-banding. By fluorescence in situ hybridization (FISH) with YAC and cosmid probes we could further characterize the breakpoint region on the X chromosome and the involvement of the factor IX gene.

Position effect of translocations involving the inactive X chromosome: physical linkage to XIC/XIST does not lead to long-range de novo inactivation in human differentiated cells

“…However, humans do not tolerate extreme genetic imbalance (Keitges and Palmer, 1986;Schmidt and Du Sart, 1992). This is the reason why in inherited X/autosome translocations the structurally normal X chromosome is usually the one that is inactivated (see Schroder et al, 1997, andPuck andWillard, 1998). However, the constitutive X/ autosome translocations analyzed in those studies were already present before the initiation of X inactivation at the early embryonic stage, and, because of positive selection toward cells carrying inactive, nontranslocated X chromosomes, these patients cannot be used to study de novo-induced inactivation in differentiated somatic cells.…”

Molecular Analysis of Factor IX Gene in an Iranian Female with Severe Hemophilia B

“…Also, a few cases with cytogenetic aberrations like translocations between X and an autosomal chromosome have been reported [16, 17]. …”

Chapter 1 Profiling of Mutations in the F8 and F9, Causative Genes of Hemophilia A and Hemophilia B"

“…In particular, a balanced chromosomal rearrangement involving the F9 gene on the Xq27.1 band disrupts the normal transcription and translation of the molecule, leading to HB. Karyotype analyses using peripheral blood lymphocytes can detect rearrangements such as t(X;1)(q27.1;q22 or q23) and t(X;15)(q27.1;p11.2) (Ghosh et al, 2009;Schroder, W. et al, 1998). In particular, these rearrangements can be the genetic backgrounds of female HB with or without family history.…”