Disease relevance of Xmmv62

• Twenty known cases of X;autosome translocations with breakpoints at Xp21 associated with Duchenne or Becker muscular dystrophy in girls are reviewed [1].
• Deletion mutations and linkage mapping have localized an X-linked retinitis pigmentosa locus to Xp21, and a disease gene (RPGR) has been characterized [2].
• Biochemical abnormalities have been reported in dystrophin-deficient muscle of boys with Duchenne (severe Xp21) muscular dystrophy or in the murine (mdx) model of the disease [3].
• Current status of research on the Xp21 myopathies [4].

High impact information on Xmmv62

• DAX1, which encodes an unusual member of the nuclear hormone-receptor superfamily, is a gene that may be responsible for a sex-reversal syndrome in humans, referred to as dosage-sensitive sex reversal, in which XY individuals carrying duplications of Xp21, part of the small arm of the X chromosome, develop as females [5].
• Localization of DNA sequences in region Xp21 of the human X chromosome: search for molecular markers close to the Duchenne muscular dystrophy locus [6].
• High resolution cytogenetic studies on 12 cases indicate breakpoints on the X chromosome at Xp21.1 or Xp21 [1].
• This NMJ-associated homologue of dystrophin has at least 2 epitopes which are different to usual Xp21 form of dystrophin expressed along the sarcolemma of muscle fibres in normal muscles [7].
• 1. (Our results suggest the following order of loci in Xp21-p22: cen-DMD-[GK,AHC]-DXS67 (pB24)-POLA-ZFX-[DXS41 (p99-6), DXS274 (CRI-L1391)]-DXS43 (pD2)-pter.) These findings contradict the model that escape from X inactivation is limited to genes near the short-arm telomere (i.e., in Xp22.3) [8].

Biological context of Xmmv62

• The gene responsible for the disease has been cloned from knowledge of its map location at band Xp21 on the short arm of the X chromosome [9].
• These two hybrids in combination with a third (WAG 8) retaining Xqter to Xp21 as a human X-autosome translocation chromosome, form a mapping panel for rapid subregional assignments to the human X chromosome [10].
• In both forms of muscular dystrophy, the severe Duchenne's muscular dystrophy (DMD) with lifespan shortened to about 20 years and the milder Becker dystrophy (BDM) with normal lifespan, the gene defect is located at chromosome locus Xp21 [11].

Anatomical context of Xmmv62

• A series of cell lines with X chromosome abnormalities was used to localize the gene to band Xp21 [12].
• In humans, a partial Xp21 duplication leads to the development of ovaries instead of testes in XY individuals [13].
• Dystrophin, a product of a gene located at the chromosome Xp21 locus, is a cytoskeletal protein expressed in skeletal, cardiac and smooth muscles, and in the brain, and is located on the inner site of the plasma membrane [14].

References