title: Börjeson-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.
authors.affiliation: Department of Hygiene and Medical Genetics, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kubota
authors.forename: S
authors.initials: S
authors.lastname: Oga
authors.forename: H
authors.initials: H
authors.lastname: Ohashi
authors.forename: Y
authors.initials: Y
authors.lastname: Iwamoto
authors.forename: Y
authors.initials: Y
authors.lastname: Fukushima
mesh_terms: D000328:Adult; D004303:Dosage Compensation, Genetic; D004827:Epilepsy / Q000235:genetics*; D005145:Face / Q000002:abnormalities; D005260:Female; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D009123:Muscle Hypotonia / Q000235:genetics; D009765:Obesity / Q000235:genetics*; D016133:Polymerase Chain Reaction; D013577:Syndrome; D014960:X Chromosome / Q000235:genetics*