MTM1 mutations in X‐linked myotubular myopathy

  title={MTM1 mutations in X‐linked myotubular myopathy},
  author={Jocelyn Laporte and Val{\'e}rie Biancalana and Stephan M. Tanner and Wolfram Kress and Vreni Schneider and Carina Wallgren‐Pettersson and Franziska Herger and Anna Buj‐Bello and François Blondeau and Sabina Liechti‐Gallati and J. L. Mandel},
  journal={Human Mutation},
X‐linked myotubular myopathy (XLMTM; MIM# 310400) is a severe congenital muscle disorder caused by mutations in the MTM1 gene. This gene encodes a dual‐specificity phosphatase named myotubularin, defining a large gene family highly conserved through evolution (which includes the putative anti‐phosphatase Sbf1/hMTMR5). We report 29 mutations in novel cases, including 16 mutations not described before. To date, 198 mutations have been identified in unrelated families, accounting for 133 different… 

Pathogenic Mechanisms in Centronuclear Myopathies

An overview of clinical, histopathological, and genetic aspects of the CNMs in the context of the key pathogenic mechanism is provided, unresolved questions are outlined, and promising future lines of enquiry are indicated.

X‐linked myotubular myopathy: mutation R69C identified in a family with multiple neonatal deaths

X-linked myotubular myopathy (XL-MTM, MIM#310400) is an X-linked congenital myopathy characterized by muscle weakness, marked hypotonia and respiratory impairment at birth, in which a previously reported ‘mild missense mutation’ (R69C) is associated with multiple neonatal deaths.

Two Cases of X-Linked Myotubular Myopathy with Novel MTM1 Mutations

Genetic testing for MTM1 is helpful for the differential diagnosis of floppy male infants and it is suggested that advanced molecular genetic testing may permit a correct diagnosis while avoiding invasive procedures.

X-linked recessive myotubular myopathy with MTM1 mutations

A newborn who required intubation and ventilator care because of profound hypotonia and respiratory difficulty was experienced, and an MTM1 gene mutation of c.1261-1C>A in the intron 10 region was detected, and the neonate was diagnosed with myotubular myopathy.

Characterisation of mutations in 77 patients with X-linked myotubular myopathy, including a family with a very mild phenotype

The spectrum of mutations in the MTM1 gene is enlarged from the very severe classic neonatal phenotype to very mild phenotype allowing survival to the age of 67 years, and a missense mutation N180K is identified in a 67-year-old grandfather, previously suspected to have autosomal centronuclear myopathy.

Characterization of mutations in fifty North American patients with X‐linked myotubular myopathy

X‐linked myotubular myopathy (MTM1) is a rare developmental disorder of skeletal muscle that is characterized by the presence of abnormal central nuclei in biopsy specimens taken from affected

Myotubular myopathy caused by multiple abnormal splicing variants in the MTM1 RNA in a patient with a mild phenotype

It is concluded that the analysis of RNA by RT-PCR and sequencing is an important step to characterize the precise impact of detected splice variants, and it is likely that complex splice aberrations due to a single mutation also account for unsolved cases in other diseases.

Diagnosis of X‐linked myotubular myopathy by detection of myotubularin

Immunoprecipitation of myotubularin from cultured cells represents a rapid and helpful method for classifying those cases where no mutation was found, and the amount of expression may be of diagnostic value for disease course in patients with a mutation.

X-linked myotubular myopathy due to a complex rearrangement involving a duplication of MTM1 exon 10




Germline mosaicism in X‐linked myotubular myopathy

Two brothers affected with XLMTM are shown to have a point mutation (G1187A) in exon 11 of the MTM1 gene, which is the third report of germline mosaicism inXLMTM, which has important implications for genetic counseling.

Mutations in the MTM1 gene implicated in X-linked myotubular myopathy. ENMC International Consortium on Myotubular Myopathy. European Neuro-Muscular Center.

More than half of XLMTM mutations are expected to inactivate the putative enzymatic activity of myotubularin, either by truncation or by missense mutations affecting the predicted PTP domain, thus indicating the presence of other functional domains.

Identification of novel mutations in the MTM1 gene causing severe and mild forms of X‐linked myotubular myopathy

The identification of 21 mutations (14 novel) in XLMTM patients are described and four mutations—three missense (R241C, I225T, and novel mutation P179S) and one single‐amino acid deletion (G294del)—were found in patients with a much milder phenotype.

Characterization of mutations in the myotubularin gene in twenty six patients with X-linked myotubular myopathy.

The identification of mutations in 26 of 41 independent male patients with muscle biopsy-proven MTM, by direct genomic sequencing of 92% of the known coding sequence of the myotubularin gene, suggests that direct mutation screening for molecular diagnosis may require gene sequencing.

A gene mutated in X–linked myotubular myopathy defines a new putative tyrosine phosphatase family conserved in yeast

The presence of frameshift or missense mutations in seven patients proved that one of these genes is indeed implicated in MTM1, a new family of putative tyrosine phosphatases in man.

Genomic organization of the MTM1 gene implicated in X-linked myotubular myopathy

A new polymorphic marker in the immediate vicinity of the MTM1 gene is characterised, which might prove useful for linkage analysis and Sequencing of the TATA-less predicted promoter provides the basis for transcriptional regulatory studies.

[X-linked recessive myotubular myopathy with a splice-site mutation in the myotubularin gene].

A male patient with X-linked myotubular myopathy in whom MTM 1 gene mutation was first identified in Japan had 9-nucleotide insertion between exons 11 and 12 due to aberrant splicing, and whether these findings were causally related to the splice-site mutation remained obscure.

Confirmation of prenatal diagnosis results of X‐linked recessive myotubular myopathy by mutational screening, and description of three new mutations in the MTM1 gene

Direct mutational diagnosis of families at risk in combination with haplotype analysis avoid the drawbacks using only linkage analysis, make genetic counselling far more reliable, and early clinical management of this disease more appropriate.