X-linked Myotubular Myopathy: a Novel Mutation in the MTM-1 Gene –⁠ Case Reports

Czech version

Authors: P. Laššuthová ¹; V. Sebroň ²; J. Zámečník ³; J. Haberlová ¹; A. Baxová ⁴; P. Seeman ¹
Authors‘ workplace: DNA laboratoř Kliniky dětské neurologie 2. LF UK a FN v Motole, Praha ¹; Novorozenecké oddělení Gynekologicko-porodnické kliniky 1. LF UK a VFN v Praze ²; Ústav patologie a molekulární medicíny 2. LF UK a FN v Motole, Praha ³; Ústav biologie a lékařské genetiky 1. LF UK a VFN v Praze ⁴
Published in: Cesk Slov Neurol N 2013; 76/109(2): 241-245
Category: Case Report

Overview

Mutations in the MTM1 gene cause X-linked myotubular myopathy (XLMTM). This is a serious, often lethal, condition. We report a family with two affected children –⁠ dizygotic twins. Boys were born in the 28^th gestational week. Severe hypotonia and muscle weakness were present at birth and necessitated ventilatory support. Intensive care was terminated 26 and 35 days after birth, respectively, due to cardiac and renal failure. Hypotrophic muscle fibers, fetal myotubes and centrally located nuclei were present in muscle sections. All the available information led us to the diagnosis of XLMTM. The MTM1 gene was sequenced and a novel mutation c.82delA in exon 3 was identified. The mother of the patients is a heterozygous carrier of the mutation. This might well be the first report of genetically confirmed XLMTM in the Czech Republic. DNA test is now available and prenatal or preimplantation diagnosis might be offered to the family.

Key words:
MTM1 gene –⁠ myotubular myopathy –⁠ frameshift mutation

Sources

1. Romero NB, Bitoun M. Centronuclear myopathies. Semin Pediatr Neurol 2011; 18(4): 250–256.

2. Romero NB. Centronuclear myopathies: a widening concept. Neuromuscul Disord 2010; 20(4): 223–228.

3. Bijarnia S, Puri RD, Jain M, Kler N, Roy S, Urtizberea JA et al. Mutation studies in X-linked myotubular myopathy in three Indian families. Indian J Pediatr 2010; 77(4): 431–433.

4. Tosch V, Vasli N, Kretz C, Nicot AS, Gasnier C, Dondaine N et al. Novel molecular diagnostic approaches for X-linked centronuclear (myotubular) myopathy reveal intronic mutations. Neuromuscul Disord 2010; 20(6): 375–381.

5. Tachi N, Kozuka N, Chiba S, Miyaji M, Watanabe I. A double mutation in a patient with X-linked myotubular myopathy. Pediatr Neurol 2001; 24(4): 297–299.

6. McEntagart M, Parsons G, Buj-Bello A, Biancalana V, Fenton I, Little M et al. Genotype-phenotype correlations in X-linked myotubular myopathy. Neuromuscul Disord 2002; 12(10): 939–946.

7. Tanner SM, Schneider V, Thomas NS, Clarke A, Lazarou L, Liechti-Gallati S. Characterization of 34 novel and six known MTM1 gene mutations in 47 unrelated X-linked myotubular myopathy patients. Neuromuscul Disord 1999; 9(1): 41–49.

8. ExonPrimer [online]. Cited 2010-09-10. Available from: http://ihg.gsf.de/ihg/ExonPrimer.html.

9. PubMed [online]. Cited 2011-09-10. Available from: http://www.ncbi.nlm.nih.gov/pubmed/.