Medical complications in long-term survivors with X-linked myotubular myopathy

Herman, Gail E.; Finegold, Milton J.; Zhao, Wei; Gouyon, Béatrice; Metzenberg, Aı̈da

doi:10.1016/s0022-3476(99)70417-8

Cited by 173 publications

(175 citation statements)

References 17 publications

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“…During routine MTM1 gDNA sequencing in P2, no symmetrical PCR amplification was obtained for the majority of exons (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14). This led us to suspect the presence of a large intragenic deletion, which was subsequently confirmed by MLPA (Supplementary Figure S5a).…”

Section: Mtm1-lovdmentioning

confidence: 98%

“…10 Different authors have proposed that patients be classified according to their phenotype, as: (i) severecharacteristic facial features, markedly delayed motor milestones and requiring prolonged ventilatory support (412 h); (ii) moderatemore rapid acquirement of motor milestones and independent respiration for 412 h per day; (iii) mild -motor milestones slightly delayed and independent spontaneous respiratory function achieved after the neonatal period. 11,12 Carrier females are usually asymptomatic, however there are several records of manifesting heterozygotes due to skewed X chromosome inactivation. [13][14][15][16][17][18] The MTM1 gene (in Xq28) is composed of 15 exons and has an open reading frame of 1.8 kb encoding the myotubularin protein.…”

Section: Introductionmentioning

confidence: 99%

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Expanding the MTM1 mutational spectrum: novel variants including the first multi-exonic duplication and development of a locus-specific database

Oliveira

Kreß

et al. 2012

Eur J Hum Genet

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Myotubular myopathy (MIM#310400), the X-linked form of Centronuclear myopathy (CNM) is mainly characterized by neonatal hypotonia and inability to maintain unassisted respiration. The MTM1 gene, responsible for this disease, encodes myotubularin -a lipidic phosphatase involved in vesicle trafficking regulation and maturation. Recently, it was shown that myotubularin interacts with desmin, being a major regulator of intermediate filaments. We report the development of a locus-specific database for MTM1 using the Leiden Open Variation database software (http://www.lovd.nl/MTM1), with data collated for 474 mutations identified in 472 patients (by June 2012). Among the entries are a total of 25 new mutations, including a large deletion encompassing introns 2-15. During database implementation it was noticed that no large duplications had been reported. We tested a group of eight uncharacterized CNM patients for this specific type of mutation, by multiple ligationdependent probe amplification (MLPA) analysis. A large duplication spanning exons 1-5 was identified in a boy with a mild phenotype, with results pointing toward possible somatic mosaicism. Further characterization revealed that this duplication causes an in-frame deletion at the mRNA level (r.343_444del). Results obtained with a next generation sequencing approach suggested that the duplication extends into the neighboring MAMLD1 gene and subsequent cDNA analysis detected the presence of a MTM1/MAMLD1 fusion transcript. A complex rearrangement involving the duplication of exon 10 has since been reported, with detection also enabled by MLPA analysis. It is thus conceivable that large duplications in MTM1 may account for a number of CNM cases that have remained genetically unresolved.

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Section: Mtm1-lovdmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Expanding the MTM1 mutational spectrum: novel variants including the first multi-exonic duplication and development of a locus-specific database

Oliveira

Kreß

et al. 2012

Eur J Hum Genet

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“…(Hnia, Tronchere et al 2011). Although the primary and most striking phenotype of MTM1-loss-of-function affects muscle fibers, patients with a milder form of XLCNM carrying MTM1 missense mutations develop additional symptoms such as liver dysfunction (Herman, Finegold et al 1999). Thus, MTM1 function might not be restricted to muscles.…”

Section: Mtm1 Regulates Endosomal Pi(3)p Turnover and Membrane Dynamicsmentioning

confidence: 99%

“…Eluates were loaded onto a 10% acrylamide gel for SDS-PAGE followed by immunoblotting. XLCNM-patients with a mild form of the disease survive and display muscle as well as nonmuscle phenotypes (Herman, Finegold et al 1999). This argues for a more general and broader function of MTM1 in muscle and non-muscle tissue.…”

Section: Co-immunoprecipitationmentioning

confidence: 99%

A phosphoinositide conversion mechanism for exit from endosomes

Ketel¹,

Krauß²,

Nicot³

et al. 2016

Nature

162

177

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I owe special thanks to Marnix Wieffer and Michael Krauß, who spent a lot of time helping me to get started in the lab, to overcome numerous experimental problem, I was not sure how to deal with, and frequently joined in discussions about my project with excellent advice. I am really grateful for your experimental support, Michael, and the time you invested in the project during our paper revision.Further, I would like to thank Jocelyn Laporte and his group, especially Anne-Sophie Nicot, at the IGBMC in Strasbourg for their support and a very fruitful collaboration, and Carsten Schultz and his group at the EMBL in Heidelberg for their support and constant supply with PIP/AMs. I owe special thanks to Dmytro Puchkov for the ultrastructural analysis and Eberhard Krause for mass spectrometry done within this project. I also need to acknowledge Markus Wenk and Federico Torta at the Singapore Lipidomics Incubator for joining the project at a very late stage, when we urgently needed help from lipidomics specialists. It was a pity that experiments did not work out as planned.I would further like to express my gratitude to two very skilled technicians in the AG Haucke lab: Silke Zillmann and Delia Löwe. Without your help it would have been impossible to achieve so much within the limited amount of time I had during the paper revision. by VPS34-IN1 treatment................................................... 52 2.3.11 Fluorescence microscopy................................................................................. 53 2.3.12 Flow cytometry............................................................................................ III SummaryPhosphoinositides (PIs) are a minor class of short-lived phospholipids that serve as crucial signposts of membrane identity. Thereby, PIs full fill important functions in cell signaling and membrane transport. PI 4-phosphates such as phosphatitylinositol-4-phosphate (PI(4)P) and phosphatitylinositol-4,5-bisphosphate (PI(4,5)P 2 ) are enriched at the plasma membrane (PM), on secretory organelles and lysosomes, while PI 3-phosphates, i.e.phosphatitylinositol-3-phosphate (PI(3)P), are a hallmark of the endosomal system.Directional transport between these compartments, thus, requires regulated PI conversion.However, PI conversion in exit from PI(3)P-enriched endosomes en route to the PI(4)P-and PI(4,5)P 2 -positive PM in endosomal recycling remained unknown.Here, we report that cargo exit from endosomes requires removal of PI(3)P by the PI(3)P 3-phosphatase myotubularin 1 (MTM1), and concomitant PI(4)P synthesis by PI 4-kinase type II α (PI4K2α). Loss of MTM1 causes endosomal accumulation of PI(3)P and PI(3)P effector proteins, i.e. sorting nexins, Kif16b-mediated outward traffic of PI(3)P containing endosomes and sub-plasmalemmal accumulation of exocytosis-deficient endosomes. As PI4K2α associates with MTM1 and thereby facilitates membrane recruitment of MTM1, these phenotypic changes are mimicked by loss of PI4K2α. The conversion of PI(3)P-to-PI(4)P is paralleled by a switch i...

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“…La plupart des mutations touchant la desmine interfèrent avec la structure des filaments de desmine, ce qui se traduit par la formation d'agré-gats de la protéine sous forme de dépôts granulo-filamentaires [12]. Alors que les défauts de la desmine se répercutent sur les deux types de muscle, squelettique et cardiaque, des anomalies du muscle cardiaque sont absentes chez les patients XLCNM [13]. En accord avec ces données cliniques, nous avons montré que MTM1 n'interagit pas avec la desmine dans le muscle cardiaque.…”

Section: Dynamique Mitochondriale Régulée Par Mtm1 Et Le Complexe Mtmunclassified

Myotubularine et desmine

Hnia

Laporte

2011

Med Sci (Paris)

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Medical complications in long-term survivors with X-linked myotubular myopathy

Cited by 173 publications

References 17 publications

Expanding the MTM1 mutational spectrum: novel variants including the first multi-exonic duplication and development of a locus-specific database

Expanding the MTM1 mutational spectrum: novel variants including the first multi-exonic duplication and development of a locus-specific database

A phosphoinositide conversion mechanism for exit from endosomes

Myotubularine et desmine

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