Recent advances in nemaline myopathy

Laitila, J.; Wallgren‐Pettersson, Carina

doi:10.1016/j.nmd.2021.07.012

Cited by 47 publications

(63 citation statements)

References 93 publications

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“…More recently, a new classification was suggested with the aim to simplify and to give some information about the prognosis of NM patients. This classification includes the following forms: severe (intrauterine onset), typical (perinatal onset), mild (childhood or juvenile onset), distal, childhood onset with slowness, recessive TNNT1 and other forms with unusual presentation [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

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Nemaline Myopathy in Brazilian Patients: Molecular and Clinical Characterization

Gurgel-Giannetti

Souza

Yamamoto

et al. 2022

IJMS

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Nemaline myopathy (NM), a structural congenital myopathy, presents a significant clinical and genetic heterogeneity. Here, we compiled molecular and clinical data of 30 Brazilian patients from 25 unrelated families. Next-generation sequencing was able to genetically classify all patients: sixteen families (64%) with mutation in NEB, five (20%) in ACTA1, two (8%) in KLHL40, and one in TPM2 (4%) and TPM3 (4%). In the NEB-related families, 25 different variants, 11 of them novel, were identified; splice site (10/25) and frame shift (9/25) mutations were the most common. Mutation c.24579 G>C was recurrent in three unrelated patients from the same region, suggesting a common ancestor. Clinically, the “typical” form was the more frequent and caused by mutations in the different NM genes. Phenotypic heterogeneity was observed among patients with mutations in the same gene. Respiratory involvement was very common and often out of proportion with limb weakness. Muscle MRI patterns showed variability within the forms and genes, which was related to the severity of the weakness. Considering the high frequency of NEB mutations and the complexity of this gene, NGS tools should be combined with CNV identification, especially in patients with a likely non-identified second mutation.

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Section: Introductionmentioning

confidence: 99%

“…Nowadays, more than 15 genes are related to NM, including TPM3 , NEB , ACTA1 , TPM2 , TNNT1 , KBTBD13 , CFL2 (COFILIN2), KLHL40 , KLHL41 , LMOD3 , MYO18B , MYPN , RYR3 , TTN3 , ADSSL1 , Filamin C and MYH2 . Most of these genes encode structural or regulatory proteins associated with the thin filament in the skeletal muscle fiber [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Nemaline Myopathy in Brazilian Patients: Molecular and Clinical Characterization

Gurgel-Giannetti

Souza

Yamamoto

et al. 2022

IJMS

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“…NM is one of the most common of the nondystrophic congenital myopathies [ 18 ]. It is a heterogeneous disease characterized by varying degrees of skeletal muscle weakness [ 19 , 20 ]. Histologically, a diagnostic hallmark in muscle biopsies is rod-shaped protein aggregates, so-called nemaline rods, that are stained red with modified Gomori trichrome and appear as electron-dense material on electron micrographs [ 19 ].…”

Section: Introductionmentioning

confidence: 99%

Removal of MuRF1 Increases Muscle Mass in Nemaline Myopathy Models, but Does Not Provide Functional Benefits

Lindqvist

Kolb

Winter

et al. 2022

IJMS

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Nemaline myopathy (NM) is characterized by skeletal muscle weakness and atrophy. No curative treatments exist for this debilitating disease. NM is caused by mutations in proteins involved in thin-filament function, turnover, and maintenance. Mutations in nebulin, encoded by NEB, are the most common cause. Skeletal muscle atrophy is tightly linked to upregulation of MuRF1, an E3 ligase, that targets proteins for proteasome degradation. Here, we report a large increase in MuRF1 protein levels in both patients with nebulin-based NM, also named NEM2, and in mouse models of the disease. We hypothesized that knocking out MuRF1 in animal models of NM with muscle atrophy would ameliorate the muscle deficits. To test this, we crossed MuRF1 KO mice with two NEM2 mouse models, one with the typical form and the other with the severe form. The crosses were viable, and muscles were studied in mice at 3 months of life. Ultrastructural examination of gastrocnemius muscle lacking MuRF1 and with severe NM revealed a small increase in vacuoles, but no significant change in the myofibrillar fractional area. MuRF1 deficiency led to increased weights of various muscle types in the NM models. However, this increase in muscle size was not associated with increased in vivo or in vitro force production. We conclude that knocking out MuRF1 in NEM2 mice increases muscle size, but does not improve muscle function.

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“…Nemaline myopathy (NM) is a rare congenital myopathy that is a clinically and genetically heterogeneous group of disorders. Pathologically, it is a group of non-dystrophic myopathy conditions in which rod-like structures known as nemaline rods exist in skeletal muscle fibers [ 1 ]. Mutations in at least 12 genes are known to cause NM, with the most common mutations found in the genes encoding skeletal muscle alpha actin (ACTA1) and nebulin (NEB) [ 2 , 3 , 4 ].…”

Section: Introductionmentioning

confidence: 99%

Clinical Course of Dysphagia in Patients with Nemaline Myopathy

et al. 2022

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Nemaline myopathy (NM) is a rare congenital myopathy, a group of disorders that are clinically and genetically heterogeneous. Infants and children with NM often suffer from recurrent pulmonary infections and swallowing difficulty, leading to malnutrition. However, knowledge about the clinical course and prognosis of dysphagia is limited. In this study, we reported the clinical course of two NM patients suffering from dysphagia. Although tube feeding was required for several months after birth, it was eventually possible to obtain sufficient nutrition with an oral diet. Therefore, dysphagia rehabilitation therapy through a series of evaluations should be considered even in children with severe oral motor dysfunction. Through these cases, physicians should be convinced that the symptoms of dysphagia in children with NM can be improved and be able to encourage their parents by explaining this progress. They have the potential to show improvements in swallowing function and will finally be able to take food slowly but fully orally.

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Recent advances in nemaline myopathy

Cited by 47 publications

References 93 publications

Nemaline Myopathy in Brazilian Patients: Molecular and Clinical Characterization

Nemaline Myopathy in Brazilian Patients: Molecular and Clinical Characterization

Removal of MuRF1 Increases Muscle Mass in Nemaline Myopathy Models, but Does Not Provide Functional Benefits

Clinical Course of Dysphagia in Patients with Nemaline Myopathy

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