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Sarcomeric disorganization and nemaline bodies in muscle biopsies of patients with EXOSC3 ‐related type 1 pontocerebellar hypoplasia
Author(s) -
Pinto Miguel M.,
Monges Soledad,
Malfatti Edoardo,
Lubieniecki Fabiana,
Lornage Xavière,
Alias Laura,
Labasse Clémence,
Madelaine Angéline,
Fardeau Michel,
Laporte Jocelyn,
Tizzano Eduardo F.,
Romero Norma B.
Publication year - 2019
Publication title -
muscle and nerve
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.025
H-Index - 145
eISSN - 1097-4598
pISSN - 0148-639X
DOI - 10.1002/mus.26305
Subject(s) - nemaline myopathy , hypotonia , pathology , hypoplasia , medicine , spinal muscular atrophy , muscle biopsy , context (archaeology) , atrophy , anatomy , neuromuscular disease , nebulin , biology , biopsy , myopathy , sarcomere , titin , myocyte , disease , paleontology
Mutations in the EXOSC3 gene are responsible for type 1 pontocerebellar hypoplasia, an autosomal recessive congenital disorder characterized by cerebellar atrophy, developmental delay, and anterior horn motor neuron degeneration. Muscle biopsies of these patients often show characteristics resembling classic spinal muscle atrophy, but to date, no distinct features have been identified. Methods Clinical data and muscle biopsy findings of 3 unrelated patients with EXOSC3 mutations are described. Results All patients presented as a severe congenital cognitive and neuromuscular phenotype with short survival, harboring the same point mutation (c.92G>C; p.Gly31Ala). Muscle biopsies consistently showed variable degrees of sarcomeric disorganization with myofibrillar remnants, Z‐line thickening, and small nemaline bodies. Conclusions In this uniform genetic cohort of patients with EXOSC 3 mutations, sarcomeric disruption and rod structures were prominent features of muscle biopsies. In the context of neonatal hypotonia, ultrastructural studies might provide early clues for the diagnosis of EXOSC3 ‐related pontocerebellar hypoplasia. Muscle Nerve 59 :137–141, 2019