B�rjeson-Forssman-Lehmann syndrome in a woman with skewed X-chromosome inactivation

Abstract

Börjeson-Forssman-Lehmann (BFL) syndrome is an X-linked recessive disorder characterized by minor facial anomalies, obesity, epilepsy, and severe mental retardation. The phenotype of male patients is usually severe, whereas that of carriers is less severe, suggesting X-linked incompletely recessive inheritance. A recent linkage study mapped the BFL syndrome gene to Xq26-q27. The etiology of the condition in female patients with full manifestations is not known, although nonrandom X-chromosome inactivation has been considered. We recently developed an assay for X-inactivation studies based on the methylation-specific polymerase chain reaction (PCR) technique. Using the methylation-specific PCR assay, a woman with typical findings of this syndrome was shown to have an extremely skewed X-inactivation pattern. This finding suggests that the full manifestations of the BFL syndrome in carriers may be caused by skewed X inactivation with a high proportion of cells in which the X chromosome with a normal gene be inactivated, leaving the X chromosome with a mutant gene active.

Androgen receptor CAG repeats, non-random X chromosome inactivation, and loss of heterozygosity at Xq25 in relation to breast cancer risk

“…Some research suggests that women with non-random XCI are more likely to be affected by X-linked recessive diseases, such as Wiskott-Aldrich syndrome [3], Hunter’s syndrome [4], Haemophilia [5], Duchenne’s muscular dystrophy [6], and Borjeson-Forssman-Lehmann syndrome [7]. Females are carriers of X chromosome mutations and do not usually express the phenotype because the normal allele can compensate for the defect, hence men are more likely to be affected by X-linked recessive diseases.…”