title: X-linked centronuclear myopathy: mapping the gene to Xq28.
abstract: The X-linked recessive centronuclear/myotubular myopathy (XLR-CNM/MTM1), a severe neonatal disorder characterized by generalized hypotonia, muscle weakness and primary asphyxia, has recently been mapped to Xq28. This report presents linkage analysis data of eight families with X-linked centronuclear myopathy. Four probes from the region Xq26-27 and five Xq28 probes were used to get more precise gene localization and marker order. St14 (DXS52), fully informative in all families, shows significant linkage to the CNM gene (z = 3.60; theta = 0.05), followed by DX13 (DXS15) (z = 2.03; theta = 0.06) and F8 (z = 1.86; theta = 0.00). Combination of the physical map derived by Kenwrick and Gitschier (1989) and our linkage data lead to the most probable order R/GCP-G6PD-(XLR-CNM-F8)-p767-St14-cpX67-++ +DX13 placing the CNM gene close to F8. The results of this study confirm strong linkage of the CNM gene to the region Xq28 and will permit carrier testing and prenatal diagnosis in CNM families. We conclude that the precise localization of this devastating disorder may be of great importance for genetic counselling in families at risk. The lack of information about gene frequency and mutation rate as well as the severity and burden of the disease point to the inevitable need for accurate clinical diagnosis.
authors.affiliation: Department of Pediatrics (Inselspital), University of Berne, Switzerland.
authors.forename: S
authors.initials: S
authors.lastname: Liechti-Gallati
authors.forename: B
authors.initials: B
authors.lastname: Müller
authors.forename: T
authors.initials: T
authors.lastname: Grimm
authors.forename: W
authors.initials: W
authors.lastname: Kress
authors.forename: C
authors.initials: C
authors.lastname: Müller
authors.forename: E
authors.initials: E
authors.lastname: Boltshauser
authors.forename: H
authors.initials: H
authors.lastname: Moser
authors.forename: S
authors.initials: S
authors.lastname: Braga
mesh_terms: D002874:Chromosome Mapping; D004247:DNA / Q000032:analysis; D015342:DNA Probes; D005260:Female; D006580:Genetic Carrier Screening / Q000379:methods; D008040:Genetic Linkage / Q000235:genetics*; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D008126:Lod Score; D008297:Male; D009135:Muscular Diseases / Q000235:genetics*; D010375:Pedigree; D011296:Prenatal Diagnosis / Q000379:methods; D014960:X Chromosome
chemical_list: D015342:DNA Probes; D005819:Genetic Markers; D004247:DNA