Dr Heinz Jungbluth reports:
‘Mutations in the MTM1 gene are the only known genetic cause of the X-linked form of centronuclear (myotubular) myopathy but in a proportion of typically affected boys the underlying genetic defect remains elusive despite extensive investigations. Whilst some of these boys will have mutations in recently identified CNM genes – DNM2, RYR1 and BIN1 – associated with other modes of inheritance, research groups in France and the United Kingdom have now independently identified rare faults concerning the MTM1 gene which may not be detectable on routine genetic testing but will be picked up with more sophisticated techniques available in specialist laboratories. Identification of these rare faults in the MTM1 gene will help and enable counselling for families who so far have not had a precise genetic diagnosis’.
X-linked myotubular myopathy due to a complex rearrangement involving a duplication of MTM1 exon 10
Trump N, Cullup T, Verheij JB, Manzur A, Muntoni F, Abbs S, Jungbluth H.
Neuromuscul Disord. 2012 May;22(5):384-8. Epub 2011 Dec 9.
Another related article from the laboratory of Dr Jocelyn Laporte in France may also be of interest
Novel molecular diagnostic approaches for X-linked centronuclear (myotubular) myopathy reveal intronic mutations.
Tosch V, Vasli N, Kretz C, Nicot AS, Gasnier C, Dondaine N, Oriot D, Barth M, Puissant H, Romero NB, Bönnemann CG, Heller B, Duval G, Biancalana V, Laporte J.
Neuromuscul Disord. 2010 Jun;20(6):375-81.
In summary, while Dr Heinz Jungbluth’s and Dr Stephen Abb’s DNA Laboratory at Guy’s and St Thomas’ Hospital does routinely test for such changes in MTM1 sequencing negative patients with characteristic features, this is something parents of a child with MTM/CNM but no confirmed mutation ought to consider checking and discussing further with their geneticist or neuromuscular specialist. It is also important to emphasize that these unusual defects in the MTM1 gene are likely to be very rare indeed, and that it is probably as likely that a child with MTM1/CNM without confirmed genetic defect has a mutation in another, probably currently unknown gene.