The gene for X-linked myotubular myopathy is located in an 8 Mb region at the border of Xq27.3 and Xq28

Janssen, Emiel A. M.; Hensels, G. W.; Oost, B.A. van; Hamel, B.C.J.; Kemp, Stephan; Baas, Frank; Weber, Julia; Barth, P. G.; Bolhuis, P. A.

doi:10.1016/0960-8966(94)90084-1

Cited by 13 publications

(5 citation statements)

References 20 publications

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“…The X-linked recessive form ("myotubular myopathy") has been genetically well characterised. Following initial linkage studies and assignment of a locus to chromosome Xq28 [ 40 , 86 - 94 ] mutations in the myotubularin (MTM1) gene have now been identified in more than 90% of affected males [ 19 , 95 - 100 ]; molecular genetic analysis of the MTM1 gene is now widely available as a routine diagnostic service [ 34 , 101 , 102 ]. Disease-causing sequence changes include deletions/insertions, nonsense, missense and splice mutations (approximately 25% each) [ 97 , 102 ].…”

Section: Aetiologymentioning

confidence: 99%

Centronuclear (myotubular) myopathy

Jungbluth

Wallgren‐Pettersson

Laporte

2008

Orphanet J Rare Dis

267

251

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Centronuclear myopathy (CNM) is an inherited neuromuscular disorder characterised by clinical features of a congenital myopathy and centrally placed nuclei on muscle biopsy.The incidence of X-linked myotubular myopathy is estimated at 2/100000 male births but epidemiological data for other forms are not currently available.The clinical picture is highly variable. The X-linked form usually gives rise to a severe phenotype in males presenting at birth with marked weakness and hypotonia, external ophthalmoplegia and respiratory failure. Signs of antenatal onset comprise reduced foetal movements, polyhydramnios and thinning of the ribs on chest radiographs; birth asphyxia may be the present. Affected infants are often macrosomic, with length above the 90 th centile and large head circumference. Testes are frequently undescended. Both autosomal-recessive (AR) and autosomal-dominant (AD) forms differ from the X-linked form regarding age at onset, severity, clinical characteristics and prognosis. In general, AD forms have a later onset and milder course than the Xlinked form, and the AR form is intermediate in both respects. Diagnosis is based on typical histopathological findings on muscle biopsy in combination with suggestive clinical features; muscle magnetic resonance imaging may complement clinical assessment and inform genetic testing in cases with equivocal features. Genetic counselling should be offered to all patients and families in whom a diagnosis of CNM has been made.The main differential diagnoses include congenital myotonic dystrophy and other conditions with severe neonatal hypotonia.Management of CNM is mainly supportive, based on a multidisciplinary approach. Whereas the X-linked form due to MTM1 mutations is often fatal in infancy, dominant forms due to DNM2 mutations and some cases of the recessive BIN1-related form appear to be associated with an overall more favourable prognosis.

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Section: Aetiologymentioning

confidence: 99%

Centronuclear (myotubular) myopathy

Jungbluth

Wallgren‐Pettersson

Laporte

2008

Orphanet J Rare Dis

267

251

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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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“…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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The gene for X-linked myotubular myopathy is located in an 8 Mb region at the border of Xq27.3 and Xq28

Cited by 13 publications

References 20 publications

Centronuclear (myotubular) myopathy

Centronuclear (myotubular) myopathy

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

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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