Identification of a novel mutation in the MTM1 gene associated with X-linked myotubular myopathy, in a Greek family

Fidani, Liana; P, Karagianni; Tsakalidis, Christos; Mitsiakos, Georgıos; Biancalana, Valérie; Nikolaidis, Nikolas

doi:10.1016/s1090-3798(08)70178-8

Cited by 1 publication

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“…X-linked myotubular myopathy (XLMTM, OMIM 310400) is the most common and severe form of centronuclear myopathy [ 1 ], affecting approximately 1/50,000 male newborns [ 2 ]. The affected babies manifest severe hypotonia and respiratory insufficiency at birth [ 3 ], and the majority of them die during the first months of life [ 2 ]. Muscle biopsy generally shows central nuclei that are larger than normal and have a vesicular appearance [ 4 ], and it is often characterized by the presence of “necklace fibers” that are peculiar myofibrillar aggregates surrounded by mitochondria, sarcoplasmic reticulum and glycogen granules [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Novel Splicing Mutation in MTM1 Leading to Two Abnormal Transcripts Causes Severe Myotubular Myopathy

Bosco

Leone

Costa-Comellas

et al. 2022

IJMS

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X-linked myotubular myopathy (XLMTM) is a severe form of centronuclear myopathy, characterized by generalized weakness and respiratory insufficiency, associated with pathogenic variants in the MTM1 gene. NGS targeted sequencing on the DNA of a three-month-old child affected by XLMTM identified the novel hemizygous MTM1 c.1261-5T>G intronic variant, which interferes with the normal splicing process, generating two different abnormal transcripts simultaneously expressed in the patient’s muscular cells. The first aberrant transcript, induced by the activation of a cryptic splice site in intron 11, includes four intronic nucleotides upstream of exon 12, resulting in a shift in the transcript reading frame and introducing a new premature stop codon in the catalytic domain of the protein (p.Arg421SerfsTer7). The second aberrant MTM1 transcript, due to the lack of recognition of the 3′ acceptor splice site of intron 11 from the spliceosome complex, leads to the complete skipping of exon 12. We expanded the genotypic spectrum of XLMTM underlying the importance of intron–exons boundaries sequencing in male patients affected by XLMTM.

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