title: X-inactivation patterns in carriers of X-linked myotubular myopathy.
abstract: X-linked myotubular myopathy is a rare severe muscle disorder in affected male neonates. Most female carriers are free from symptoms. Skewed X inactivation has been proposed to be responsible for the affected phenotype seen in some carriers. We have compared the X inactivation patterns in blood DNA with the clinical phenotype in carriers of X-linked myotubular myopathy. The X-inactivation analysis was performed using HpaII predigestion of DNA followed by polymerase chain reaction of the highly polymorphic CAG repeat of the androgen receptor (AR) gene. The frequency of skewed X inactivation was similar in the X-linked myotubular myopathy carriers (22%) and in 235 controls (18%). Three overtly affected carriers had skewed X inactivation with the mutated X as the predominantly active X in at least two of them. Four females with mild symptoms had random X inactivation. The unaffected X-linked myotubular myopathy carriers had either skewed X inactivation in favour of expression from the normal X or random X-inactivation. Thus, there was a tendency for females with a more severe phenotype to have a skewed pattern of X inactivation, while females with an intermediate phenotype had a random pattern of X-inactivation.
authors.affiliation: Department of Medical Genetics, Institute of Medical Genetics, University of Oslo, Oslo, Norway. marianne.kristiansen@ioks.uio.no
authors.forename: M
authors.initials: M
authors.lastname: Kristiansen
authors.forename: G P
authors.initials: GP
authors.lastname: Knudsen
authors.forename: S M
authors.initials: SM
authors.lastname: Tanner
authors.forename: M
authors.initials: M
authors.lastname: McEntagart
authors.forename: H
authors.initials: H
authors.lastname: Jungbluth
authors.forename: F
authors.initials: F
authors.lastname: Muntoni
authors.forename: C
authors.initials: C
authors.lastname: Sewry
authors.forename: S
authors.initials: S
authors.lastname: Gallati
authors.forename: K H
authors.initials: KH
authors.lastname: Ørstavik
authors.forename: C
authors.initials: C
authors.lastname: Wallgren-Pettersson
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D004303:Dosage Compensation, Genetic; D005260:Female; D006579:Heterozygote; D006801:Humans; D008875:Middle Aged; D020914:Myopathies, Structural, Congenital / Q000235:genetics*; D010641:Phenotype; D011944:Receptors, Androgen / Q000235:genetics; D018911:Trinucleotide Repeats
chemical_list: D011944:Receptors, Androgen