Clinical and Histologic Findings in ACTA1 -Related Nemaline Myopathy: Case Series and Review of the Literature

Moreno, Cristiane de Araújo Martins; Neto, Osório Abath; Donkervoort, Sandra; Hu, Ying; Reed, Umbertina Conti; Oliveira, Acary; Bönnemann, Carsten G.; Zanoteli, Edmar

doi:10.1016/j.pediatrneurol.2017.04.002

Cited by 18 publications

(11 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our study showed that five of seven patients with ACTA1 gene mutations had heterozygous missense mutations. Previous studies showed that ACTA1 mutations were predominantly inherited in a de novo dominant manner 23 . However, without any confirmation regarding the paternity and maternity, none of their patients showed remarkable family history; hence, we also speculated that these were de novo mutations.…”

Section: Discussionmentioning

confidence: 75%

“…Since the first NM case was reported by Roan JC et al in 1984, 18 hereditary NM cases have been reported worldwide 10,19,20 . Genetic studies in different ethnic cohorts showed that NEB mutations were the most frequent cause of autosomal recessive NM in Korea 21 and Italy, 22 and ACTA1 was the second most common hereditary NM gene in Brazil 23 . However, limited data were available regarding cases of NM from mainland China until now 24‐27 …”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Mutational and clinical spectrum in a cohort of Chinese patients with hereditary nemaline myopathy

Wang

Chang

et al. 2020

Clinical Genetics

View full text Add to dashboard Cite

Hereditary nemaline myopathy (NM) is one of the most common congenital myopathies with the histopathological findings of nemaline bodies. We used targeted nextgeneration sequencing to identify causative mutations in 48 NM patients with confirmed myopathological diagnosis, analyze the mutational spectrum and phenotypic features. Furthermore, reverse transcription polymerase chain reaction (RT-PCR) was used to confirm the pathogenic effect of one nebulin (NEB) splicing variant. The results showed that variants were found in five NM-associated genes, including NEB, actin alpha 1 (ACTA1), troponin T1, Kelch repeat and BTB domain-containing 13, and cofilin-2, in 34 (73.9%), 7 (15.2%), 3 (6.5%), 1 (2.2%), and 1 (2.2%) patients, respectively, in a total of 46/48 (95.8%) NM patients. Of the total 64 variants identified, 51 were novel variants including 26 pathogenic, 1 probably pathogenic, and 24 variant of uncertain significance (VUS). Notably, one NEB splicing mutation, c.21417 +3A>G causing exon 144 splicing (NM_001164508.1), as confirmed by RT-PCR, was found in 52.9% (18 patients) of NEB variant-carrying patients. Typical congenital NM, the most common clinical subtype (60.4%), was associated with five NM genes. We concluded that hereditary NM showed a highly variable genetic spectrum. NEB was the most frequent causative gene in this Chinese cohort, followed by ACTA1. We found a hotspot splicing mutation in NEB among Chinese cohort. K E Y W O R D SChinese, genotype, hereditary nemaline myopathy, phenotype

show abstract

Section: Discussionmentioning

confidence: 75%

Section: Introductionmentioning

confidence: 99%

Mutational and clinical spectrum in a cohort of Chinese patients with hereditary nemaline myopathy

Wang

Chang

et al. 2020

Clinical Genetics

View full text Add to dashboard Cite

show abstract

“…NEB mutations are usually recessively inherited, but recently, the first dominantly inherited mutation was identified in NEB , causing a distal form of nemaline myopathy (Kiiski et al 2019). A great number of different mutations have been identified in these two genes (Sparrow et al 2003; Feng and Marston 2009; Nowak et al 2013; Lehtokari et al 2014; Moreno et al 2017).…”

Section: Geneticsmentioning

confidence: 99%

Nemaline myopathies: a current view

Sewry

Laitila

Wallgren‐Pettersson

2019

J Muscle Res Cell Motil

135

133

View full text Add to dashboard Cite

Nemaline myopathies are a heterogenous group of congenital myopathies caused by de novo, dominantly or recessively inherited mutations in at least twelve genes. The genes encoding skeletal α-actin (ACTA1) and nebulin (NEB) are the commonest genetic cause. Most patients have congenital onset characterized by muscle weakness and hypotonia, but the spectrum of clinical phenotypes is broad, ranging from severe neonatal presentations to onset of a milder disorder in childhood. Most patients with adult onset have an autoimmune-related myopathy with a progressive course. The wide application of massively parallel sequencing methods is increasing the number of known causative genes and broadening the range of clinical phenotypes. Nemaline myopathies are identified by the presence of structures that are rod-like or ovoid in shape with electron microscopy, and with light microscopy stain red with the modified Gömöri trichrome technique. These rods or nemaline bodies are derived from Z lines (also known as Z discs or Z disks) and have a similar lattice structure and protein content. Their shape in patients with mutations in KLHL40 and LMOD3 is distinctive and can be useful for diagnosis. The number and distribution of nemaline bodies varies between fibres and different muscles but does not correlate with severity or prognosis. Additional pathological features such as caps, cores and fibre type disproportion are associated with the same genes as those known to cause the presence of rods. Animal models are advancing the understanding of the effects of various mutations in different genes and paving the way for the development of therapies, which at present only manage symptoms and are aimed at maintaining muscle strength, joint mobility, ambulation, respiration and independence in the activities of daily living.

show abstract

“…To date, more than 200 different pathogenic variants have been identified in the α-actin 1 gene (ACTA1). The vast majority, over 170 of these disease-causing variants, cause nemaline myopathy (NM), but variants in ACTA1 may cause a wide spectrum of myopathies, clinically varying from lethal fetal akinesia to disorders with mild muscle weakness [1,2]. In addition to NM, ACTA1 myopathies include actin myopathy, cap myopathy, congenital fibre-type disproportion, core-rod myopathy, intranuclear rod myopathy, zebra body myopathy, and progressive scapuloperoneal myopathy.…”

Section: Introductionmentioning

confidence: 99%

Clinically variable nemaline myopathy in a three-generation family caused by mutation of the skeletal muscle alpha-actin gene

Lehtokari

Gardberg

Pelin

et al. 2018

Neuromuscular Disorders

View full text Add to dashboard Cite

We present here a Finnish nemaline myopathy family with a dominant mutation in the skeletal muscle α-actin gene, p.(Glu85Lys), segregating in three generations. The index patient, a 5-year-old boy, had the typical form of nemaline myopathy with congenital muscle weakness and motor milestones delayed but reached, while his mother never had sought medical attention for her very mild muscle weakness, and his maternal grandmother had been misdiagnosed as having myotonic dystrophy. This illustrates the clinical variability in nemaline myopathy.

show abstract

Clinical and Histologic Findings in ACTA1 -Related Nemaline Myopathy: Case Series and Review of the Literature

Cited by 18 publications

References 29 publications

Mutational and clinical spectrum in a cohort of Chinese patients with hereditary nemaline myopathy

Mutational and clinical spectrum in a cohort of Chinese patients with hereditary nemaline myopathy

Nemaline myopathies: a current view

Clinically variable nemaline myopathy in a three-generation family caused by mutation of the skeletal muscle alpha-actin gene

Contact Info

Product

Resources

About