Nemaline myopathy type 6: Clinical and myopathological features

Institute of Neuropathology, Pathology Department, IDIBELL-Hospital de Bellvitge and CIBERNED, Hospitalet de Llobregat, Feixa Llarga s/n, Hospitalet de Llobregat, Barcelona 08907, Spain.
Muscle & Nerve (Impact Factor: 2.28). 12/2010; 42(6):901-7. DOI: 10.1002/mus.21788
Source: PubMed


Nemaline myopathy (NEM) is one of the most common congenital myopathies. A unique subtype, NEM6, maps to chromosome 15q21-q23 in two pedigrees, but the causative gene has not been determined. We conducted clinical examination and myopathological studies in a new NEM family. Genotyping and gene screening were accomplished by searching known and 18 new candidate genes. The disease started in childhood by affecting proximal and distal muscles and causing slowness of movements. Muscle biopsies showed numerous nemaline rods and core-like formations. Suggestive linkage to chromosome 15q22-q23 was established. Genes known to be mutated in NEM or core-rod myopathy were screened and excluded. No pathogenic mutations were identified in other candidate genes. The disease in this Spanish family was classified as NEM6. It is phenotypically similar and probably allelic to the two previously reported NEM6 pedigrees. Further studies of these families will lead to the identification of the NEM6 gene.

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    • "It has been increasingly recognized that the histological features observed within a muscle biopsy may represent manifestations along spectra of possible abnormalities, rather than discrete pathological entities (Sewry et al., 2008; Nance et al., 2012). For example central nuclei are classically associated with mutations in BIN1, DNM2, MTM1, and SPEG however, more recently, prominent central nuclei have been reported in cases resulting from mutations in CFL2 (Ockeloen et al., 2012), KBTBD13 (Olive et al., 2010), RYR1 (Wilmshurst et al., 2010) and TTN (Ceyhan-Birsoy et al., 2013; Palmio et al., 2014). On the flip side, although congenital myopathies have traditionally been classified purely by their defining histopathology , with the discovery of the underlying genetic cause for an increasing number of patients, the field has also begun in parallel to classify patients based on the causative disease gene, such that there is now, for instance, reference to ACTA1-related myopathies (Nowak et al., 2013), RYR1-related myopathies (Klein et al., 2012; Amburgey et al., 2013; Bharucha-Goebel et al., 2013) and SEPN1- related myopathies (Schara et al., 2008; Scoto et al., 2011). "
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