A linkage study of a large pedigree with X linked centronuclear myopathy.

Starr, John M.; Lamont, M A; Iselius, Lennart; Harvey, John F.; Heckmatt, J. Z.

doi:10.1136/jmg.27.5.281

Cited by 27 publications

(7 citation statements)

References 6 publications

(1 reference statement)

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“…Previous studies have shown evidence for linkage between MTM1 and several polymorphic DNA markers at Xq28 (Thomas et al 1987;Darnfors et al 1990;Lehesjoki et al 1990;Starr et al 1990; Thomas et al 1990;Liechti-Gallati et al 1991;Janssen et al 1994). A more precise relative localization of the MTM1 gene and other marker loci was achieved after analysis of key recombinations (Dahl et al 1994) and an interstitial deletion associated with MTM1 (Dahl et al 1995).…”

Section: Introductionmentioning

confidence: 99%

X-linked myotubular myopathy: refinement of the gene to a 280-kb region with new and highly informative microsatellite markers

Laporte

Kioschis

et al. 1996

Human Genetics

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We have recently refined the localization of the myotubular myopathy (MTM1) gene to a 430-kb region between DXS304 and DXS1345 in proximal Xq28. We report two new polymorphic microsatellite markers, DXS8377 and DXS7423, that were physically mapped within the critical interval. A recombination event in a family segregating for MTM1 placed the disease gene telomeric to the trinucleotide polymorphism DXS8377. Together with the recent mapping of two microdeletions associated with MTM1, the recombination refines the critical region to 280 kb. A second recombination event was observed distal to the tetranucleotide repeat DXS7423. This recombination has occurred in the off-spring of a female with a more than 67% probability of being a carrier and very likely restricts the MTM1 gene to a 130-kb region. This physical refinement is significant for positional cloning of the disease gene. The highly polymorphic markers and the precise localization of the MTM1 gene will facilitate genetic diagnosis of the disorder.

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Section: Introductionmentioning

confidence: 99%

X-linked myotubular myopathy: refinement of the gene to a 280-kb region with new and highly informative microsatellite markers

Laporte

Kioschis

et al. 1996

Human Genetics

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“…Linkage studies have mapped the XLMTM locus (MTM1) to Xq28 [10–12], and the MTM1 gene was subsequently isolated by positional cloning [13]. The gene codes for a protein named myotubularin, which appears to be ubiquitously expressed, with a 3.9 kb transcript detected in all adult and fetal tissues studied.…”

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confidence: 99%

Germline mosaicism in X‐linked myotubular myopathy

1999

Clinical Genetics

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X-linked myotubular myopathy (XLMTM; OMIM310400) is a congenital muscle disorder characterized by severe hypotonia and respiratory insufficiency. The disorder was mapped to Xq28 by linkage studies and the MTM1 gene was isolated by positional cloning. The gene product is a 603 amino acid protein named myotubularin. A small domain in its sequence shows high homology to a consensus active site of tyrosine phosphatases, a diverse class of proteins involved in signal transduction, control of cell growth, and differentiation. In this report, two brothers affected with XLMTM are shown to have a point mutation (G1187A) in exon 11 of the MTM1 gene. Surprisingly, their mother does not have this mutation in her lymphocytes. Therefore, she likely has a germline mosaicism. As this is the third report of germline mosaicism in XLMTM, the finding has important implications for genetic counseling.

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“…The MTM1 gene has been mapped to the Xq28 region of the long arm of the X chromosome (Darnfors et al 1990;Janssen et al 1994;Lehesjoki et al 1990;Liechti-Gallati et al 1991;Starr et al 1990;Thomas et al 1987Thomas et al , 1990. Subsequent genetic linkage studies have refined its localization, reducing the candidate region to a 430-kb interval, distal to DXS304 .…”

Section: Discussionmentioning

confidence: 99%

“…Subsequent genetic linkage studies have confirmed the assignment of the gene (Darnfors et al 1990;Janssen et al 1994;Lehesjoki et al 1990;Liechti-Gallati et al 1991;Starr et al 1990), refining the candidate region subsequently to a 600-kb interval (Dahl et al 1995) and narrowing it recently to about 430 kb, distal to DXS304 ; Fig. 1).…”

Section: Introductionmentioning

confidence: 99%

Detection of a new polymorphism in the plasma-membrane Ca 2+ ATPase isoform-3 gene and its exclusion as a candidate for X-linked myotubular myopathy (MTM1)

Smolenicka¹,

Guerini

Carafoli

et al. 1996

Human Genetics

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The severe neonatal centronuclear/myotubular myopathy (XLMTM) is an X-linked disorder characterized by generalized muscle weakness, hypotonia and serious respiratory insufficiency. The gene for this disease has been assigned to the long arm of chromosome X in the Xq28 band. Ca2+ ATPase isoform-3 (ATP2B3) has also been mapped to the human Xq28 region. Moreover, it is expressed in fetal but not in adult muscle, suggesting the developmental regulation of gene transcription. These findings render the ATP2B3 gene as an interesting candidate gene for XLMTM. Four families and 7 unrelated XLMTM patients have been analysed by using cDNA and genomic probes of ATP2B3. No large deletions or duplications have been found but a new EcoRI polymorphism has been identified. In addition, the DNA of an XLMTM male deletion patient has been hybridized with the ATP2B3 gene sequences. Our results therefore support the exclusion of ATP2B3 as the causal disease gene of XLMTM. The isolation of the MTM1 gene has recently been reported by another group. However, our approach has led to the detection of a new polymorphism that is an informative marker for linkage and mutation studies in other Xq28-mapped neurological or neuromuscular disorders.

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A linkage study of a large pedigree with X linked centronuclear myopathy.

Cited by 27 publications

References 6 publications

X-linked myotubular myopathy: refinement of the gene to a 280-kb region with new and highly informative microsatellite markers

X-linked myotubular myopathy: refinement of the gene to a 280-kb region with new and highly informative microsatellite markers

Germline mosaicism in X‐linked myotubular myopathy

Detection of a new polymorphism in the plasma-membrane Ca 2+ ATPase isoform-3 gene and its exclusion as a candidate for X-linked myotubular myopathy (MTM1)

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