Dynamin 2 homozygous mutation in humans with a lethal congenital syndrome

Koutsopoulos, Olga S.; Kretz, Christine; Weller, Claudia M; Roux, Aurélien; Mojzisova, Halina; Böhm, Johann; Koch, Catherine; Toussaint, Anne; Heckel, Émilie; Stemkens, Daphne; Horst, Simone A. J. ter; Thibault, Christelle; Koch, Marc; Mehdi, S. Qasim; Bijlsma, Emilia K.; Mandel, Jean‐Louis; Vermot, Julien; Laporte, Jocelyn

doi:10.1038/ejhg.2012.226

Cited by 54 publications

(39 citation statements)

References 23 publications

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“…All DNM2 mutations are either dominant or de novo missense mutations, suggesting a potentially toxic gain-of-function effect produced by the mutations. This hypothesis is supported by the observation that nonsense mutations in DNM2 that result in haploinsufficiency do not cause disease [51]. However, several studies have shown that loss of basic DNM2 functions (such as the regulation of endocytosis) occurs with some mutations, suggesting that loss of function may also contribute to the disease mechanism.…”

Section: What Causes It?mentioning

confidence: 90%

Triadopathies: An Emerging Class of Skeletal Muscle Diseases

2014

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The triad is a skeletal muscle substructure responsible for the regulation of excitation-contraction coupling. It is formed by the close apposition of the T-tubule and the terminal sarcoplasmic reticulum. A rapidly growing list of skeletal myopathies, here referred to as triadopathies, are caused by gene mutations in components of the triad. These disorders, at their root, are caused by defects in excitation contraction coupling and intracellular calcium homeostasis. Secondary abnormalities in triad structure and/or function are also reported in several muscle diseases, most notably certain muscular dystrophies. This review highlights the current understanding of both primary and secondary triadopathies, and identifies important concepts yet to be fully addressed in the field. The emphasis of the review is both on the pathogenesis of triadopathies and their potential treatment.

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Section: What Causes It?mentioning

confidence: 90%

Triadopathies: An Emerging Class of Skeletal Muscle Diseases

2014

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“…It has been reported that DNM2 gene mutation is an important factor for patients with autosomal dominant centronuclear myopathy (20) and Alzheimer's disease (21,22). Recurrent DNM2 mutations have also been identified in patients with ETP-ALL by whole-exome sequencing (6,10,23). These mutations include: E78fs in the Ras-like GTPase domain; L3354P, R364C, K382E, T404N and E468 * in the dynamin MD domain; S528fs, E544fs and K557_K558>K in the PH domain; S698L in the GTPase effector domain; and K770 * , P791T, L789fs and I805fs in the C-terminus.…”

Section: Discussionmentioning

confidence: 99%

Novel dynamin 2 mutations in adult T-cell acute lymphoblastic leukemia

Zhao

et al. 2016

Oncology Letters

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Abstract. Genetic mutations on signaling pathways are found in patients with T-cell acute lymphoblastic leukemia (T-ALL) and act as markers of high-risk leukemia. Mutations in dynamin 2 (DNM2) have been reported in T-ALL, particularly in early T-cell precursor-ALL. In the present study, DNM2 mutations were screened by sequencing DNM2 exons obtained by polymerase chain reaction amplification and gel purification in adult T-ALL patients. A total of 4 novel DNM2 mutations were identified in adult T-ALL patients, with a mutation rate of 9.5%, and the DNM2 mutations were found to co-exist with NOTCH1 and PHD finger protein 6, and were also associated with high-risk leukemia. A high rate of silent mutation was also found in the patients, but no significant association was found between the silent mutations and patients' clinical features. The present findings suggested the DNM2 mutations may be involved in the oncogenesis of T-ALL.

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“…LCCS2 is caused by mutation of ERBB3 (Narkis et al, 2007b), a member of the ERBB family of receptor tyrosine kinases; LCCS3 is caused by mutation of PIP5K1C (Narkis et al, 2007a), which encodes phosphatidylinositol-4-phosphate 5-kinase, type I, gamma (PIPKIγ); LCCS5 is caused by homozygous Dynamin 2 (DNM2) mutation (Koutsopoulos et al, 2013); while another study linked mutations in CNTNAP1 (encoding contactin associated protein 1) and ADCY6…”

Section: Introductionmentioning

confidence: 99%

Deficiency in the mRNA export mediator Gle1 impairs Schwann cell development in the zebrafish embryo

et al. 2016

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-GLE1 mutations cause lethal congenital contracture syndrome 1 (LCCS1), a severe autosomal recessive fetal motor neuron disease, and more recently have been associated with amyotrophic lateral sclerosis (ALS). The gene encodes a highly conserved protein with an essential role in mRNA export. The mechanism linking Gle1 function to motor neuron degeneration in humans has not been elucidated, but increasing evidence implicates abnormal RNA processing as a key event in the pathogenesis of several motor neuron

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Dynamin 2 homozygous mutation in humans with a lethal congenital syndrome

Cited by 54 publications

References 23 publications

Triadopathies: An Emerging Class of Skeletal Muscle Diseases

Triadopathies: An Emerging Class of Skeletal Muscle Diseases

Novel dynamin 2 mutations in adult T-cell acute lymphoblastic leukemia

Deficiency in the mRNA export mediator Gle1 impairs Schwann cell development in the zebrafish embryo

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