Two Cases of X-Linked Myotubular Myopathy with NovelMTM1Mutations

Abstract

BackgroundMyotubular myopathy (MTM) is a congenital myopathy characterized by centrally placed nuclei in muscle fibers. Mutations in the myotubularin 1 gene (MTM1) have been identified in the most of the patients with the X-linked recessive form.Case ReportThis report describes two male infants with X-linked MTM (XLMTM). Both patients presented with generalized hypotonia and respiratory difficulties since birth. We did not perform a muscle biopsy in either patient, but their conditions were diagnosed by genetic testing of MTM1. One splicing mutation, c.63+1G>C, and a frame-shift mutation, c.473delA (p. Lys158SerfxX28), were identified. Neither mutation has been reported previously.ConclusionsGenetic testing for MTM1 is helpful for the differential diagnosis of floppy male infants. We suggest that advanced molecular genetic testing may permit a correct diagnosis while avoiding invasive procedures.

Clinical Phenotype of X‐Linked Myotubular Myopathy in Labrador Retriever Puppies

“…Affected male infants are clinically abnormal at or even before birth, exhibiting decreased muscle tone, decreased movement, and areflexia 5, 21, 22. Tube feeding usually is required because of impaired ability to suck and swallow.…”

“…Tube feeding usually is required because of impaired ability to suck and swallow. Respiratory muscle weakness is severe, often requiring mechanical ventilation and complications related to ventilation cause death in many patients during infancy or early childhood 5, 21, 22. Diagnosis is based on typical histopathologic findings on muscle biopsy in combination with suggestive clinical features.…”

“…The incidence is estimated at 1/50000 male births 5, 22. Over 200 different spontaneous deletion, insertion, nonsense, missense, and splice mutations have been found in the MTM1 gene, with the majority occurring in exons 12, 4, 11, 8, and 9 5.…”

High-Content Genome-Wide RNAi Screen RevealsCCR3as a Key Mediator of Neuronal Cell Death

“…Lentiviral siRNAs for these genes were individually prepared and used to infect primary cultured cortical neurons at 7 days in vitro . Four genes ( Capn2 , Dedd , FASLG , and EIF2AK2 ) that have been previously linked to cell death ( Zhang and Ghosh, 2002 ; Scheuner et al, 2006 ; Lee et al, 2013 ; de Oliveira et al, 2014 ) served as positive controls, and an additional 13 genes that have not been previously linked to cell death were selected at random. Confirmation of gene knockdown was confirmed by reverse-transcription (RT)-PCR ( Fig.…”

A Female Patient with Xq28 Microduplication Presenting with Myotubular Myopathy, Confirmed with a Custom-Designed X-array

“…X-linked myotubular myopathy caused by a mutation in the MTM1 gene has been reported in many instances in the past, mainly affecting male patients due to the X-linked recessive nature of the disease. 2,3,12 However, there have been a few cases of female patients with XLMTM mainly attributed to skewed X-inactivation patterns in muscle fiber cells. 7 The X-inactivation pattern observed in our patient offers an explanation of her phenotype, especially since the X-inactivation pattern on her muscle biopsy was skewed toward the duplicated allele.…”