Novel mutations in <i>DNAJB6</i> cause <scp>LGMD</scp>1D and distal myopathy in French families

Jonson, Per Harald; Palmio, Johanna; Johari, Mridul; Penttilä, Sini; Evilä, Anni; Nelson, Isabelle; Bonne, Gisèle; Wiart, Nicolas; Meyer, Vincent; Boland, Anne; Deleuze, Jean‐François; Masson, C.; Stojkovic, Tanya; Chapon, Françoise; Romero, Norma B.; Sole, Gaglianò Maria; Ferrer, Xavier; Ferreiro, Ana; Hackman, Peter; Richard, Isabelle; Udd, Bjarne

doi:10.1111/ene.13598

Cited by 22 publications

(19 citation statements)

References 26 publications

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“…Previously, both designations LGMD1D and LGMD1E have been used in the literature to refer to the DNAJB6-associated LGMD subtype. While most of the described DNAJB6 mutations lead to a LGMD phenotype, some mutations are associated with a distal phenotype [88][89][90].…”

Section: Dnajb6 Mutations In Muscle Diseasementioning

confidence: 99%

“…LGMD [89] c.287C>G p.P96R distal-proximal [86] c.287C>T p.P96L [100][101][102] c.293_295delATG p.D98del distal [89] c.298T>A p.F100I [103] c.298C>A p.F100V distal onset [88] c.346+5G>A p.G79_F115del severe, early onset [88] Reference sequences: NM_058246.4 (nucleotide), NP_490647.1 (protein).…”

Section: Pf93lmentioning

confidence: 99%

“…Early changes are central myofibrillar lesions and Z-disc streaming that proceed to severe myofibrillar disintegration, and at later stages, autophagic rimmed vacuoles can be observed [73]. The protein accumulations in human and mouse muscles may be positive for structural proteins (desmin, myotilin, α-actinin, keratin 18) [14,49,88], RNA-binding stress-granule proteins (hnRNPA1, hnRNPA2/B1, TIA1) [49,89,90], TDP-43 [86,88,90], as well as chaperones and cochaperones (HSPA8, CRYAB, HSPB8, SQSTM1, BAG3, STUB1) [14,88,89,95,98]. The rimmed vacuoles are positive for SQSTM1 and the autophagosome marker LC3 (microtubule-associated proteins 1A/1B light chain 3), illustrating their autophagic origin [14,88,95].…”

Section: Clinical and Pathological Featuresmentioning

confidence: 99%

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Neuromuscular Diseases Due to Chaperone Mutations: A Review and Some New Results

Sarparanta

Jonson

Kawan

et al. 2020

IJMS

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Skeletal muscle and the nervous system depend on efficient protein quality control, and they express chaperones and cochaperones at high levels to maintain protein homeostasis. Mutations in many of these proteins cause neuromuscular diseases, myopathies, and hereditary motor and sensorimotor neuropathies. In this review, we cover mutations in DNAJB6, DNAJB2, αB-crystallin (CRYAB, HSPB5), HSPB1, HSPB3, HSPB8, and BAG3, and discuss the molecular mechanisms by which they cause neuromuscular disease. In addition, previously unpublished results are presented, showing downstream effects of BAG3 p.P209L on DNAJB6 turnover and localization.

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Section: Dnajb6 Mutations In Muscle Diseasementioning

confidence: 99%

Section: Pf93lmentioning

confidence: 99%

Section: Clinical and Pathological Featuresmentioning

confidence: 99%

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Neuromuscular Diseases Due to Chaperone Mutations: A Review and Some New Results

Sarparanta

Jonson

Kawan

et al. 2020

IJMS

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“…A), are those due to mutations in dysferlin ( DYSF ) (also called Myoshi myopathy) and anoctamin‐5 ( ANO5 ) . Also mutations in DNAJB6 initially affect the posterior compartment leg muscles; relative sparing of the tibialis anterior can be observed even in the setting of severe distal weakness . AD mutations in myotilin ( MYOT ) manifest clinically with foot drop or calf muscle weakness, but calf muscle involvement seems to occur first and can be documented radiologically, although it may not cause functional deficits until the anterior leg muscles become weak .…”

Section: Clinical Features and Underlying Gene Defectmentioning

confidence: 99%

The unfolding spectrum of inherited distal myopathies

Milone

Liewluck

2018

Muscle and Nerve

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Distal myopathies are a group of rare muscle diseases characterized by distal weakness at onset. Although acquired myopathies can occasionally present with distal weakness, the majority of distal myopathies have a genetic etiology. Their age of onset varies from early-childhood to late-adulthood while the predominant muscle weakness can affect calf, ankle dorsiflexor, or distal upper limb muscles. A spectrum of muscle pathological changes, varying from nonspecific myopathic changes to rimmed vacuoles to myofibrillar pathology to nuclei centralization, have been noted. Likewise, the underlying molecular defect is heterogeneous. In addition, there is emerging evidence that distal myopathies can result from defective proteins encoded by genes causative of neurogenic disorders, be manifestation of multisystem proteinopathies or the result of the altered interplay between different genes. In this review, we provide an overview on the clinical, electrophysiological, pathological, and molecular aspects of distal myopathies, focusing on the most recent developments in the field. Muscle Nerve, 2018.

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“…Genetic mutations or dysfunction of MRJ have been observed in human diseases such as limb-girdle muscular dystrophy (LGMD), myopathy and neurodegenerative diseases. Phenylalanine mutations in the (G/F)-rich region of MRJ are found in LGMD and distal myopathy, indicating that the chaperone activity of MRJ is critical for preventing proteinopathy (Harms et al, 2012;Sarparanta et al, 2012;Li et al, 2016;Jonson et al, 2018). MRJ mutations result in myofibrillar aggregates containing ubiquitin, ubiquitin-binding protein p62 and TAR DNA-binding protein 43 (TDP-43) (Sato et al, 2013;Sandell et al, 2016).…”

Section: Pathological Effects Of Defective Mrjmentioning

confidence: 99%

The Host Heat Shock Protein MRJ/DNAJB6 Modulates Virus Infection

Huang

Tarn

2019

Front. Microbiol.

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A variety of pathogens take advantage of cellular heat shock proteins (HSPs) to complete their life cycle and exert pathogenic effects. MRJ (DNAJB6), a member of the heat shock protein 40 family, acts as a molecular chaperone for a wide range of cellular processes. MRJ mutations are linked to human diseases, such as muscular dystrophy and neurodegenerative diseases. There are two MRJ isoforms generated by alternative use of terminal exons, which differ in their C-terminus. This mini-review summarizes how these two MRJ isoforms participate differentially in viral production and virulence, and the possibility for MRJ as a therapeutic target.

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Novel mutations in DNAJB6 cause LGMD1D and distal myopathy in French families

Cited by 22 publications

References 26 publications

Neuromuscular Diseases Due to Chaperone Mutations: A Review and Some New Results

Neuromuscular Diseases Due to Chaperone Mutations: A Review and Some New Results

The unfolding spectrum of inherited distal myopathies

The Host Heat Shock Protein MRJ/DNAJB6 Modulates Virus Infection

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