Sarcomeric disorganization and nemaline bodies in muscle biopsies of patients with EXOSC3-related type 1 pontocerebellar hypoplasia
Por:
Pinto, MM, Monges, S, Malfatti, E, Lubieniecki, F, Lornage, X, Alias, L, Labasse, C, Madelaine, A, Fardeau, M, Laporte, J, Tizzano, EF, Romero, NB
Publicada:
1 ene 2019
Resumen:
Introduction 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 EXOSC3 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
Filiaciones:
Pinto, MM:
Ctr Hosp Lisboa Ocidental, Hosp Egas Moniz, Dept Neurol, Lisbon, Portugal
Monges, S:
Natl Pediat Hosp JP Garrahan, Neuropediat Dept, Buenos Aires, DF, Argentina
Natl Pediat Hosp JP Garrahan, Dept Neuropathol, Buenos Aires, DF, Argentina
Malfatti, E:
Sorbonne Univ, Grp Hosp Univ La Pitie Salpetriere, INSERM UMR 974, Unite Morphol Neuromusculaire,Inst Myol, F-75013 Paris, France
Lubieniecki, F:
Natl Pediat Hosp JP Garrahan, Neuropediat Dept, Buenos Aires, DF, Argentina
Natl Pediat Hosp JP Garrahan, Dept Neuropathol, Buenos Aires, DF, Argentina
Lornage, X:
Univ Strasbourg, CNRS UMR7104, INSERM U1258, Dept Translat Med & Neurogenet,IGBMC, Illkirch Graffenstaden, France
Alias, L:
Hosp Santa Creu & Sant Pau, Dept Genet, Barcelona, Spain
CIBERER, Barcelona, Spain
Labasse, C:
Sorbonne Univ, Grp Hosp Univ La Pitie Salpetriere, INSERM UMR 974, Unite Morphol Neuromusculaire,Inst Myol, F-75013 Paris, France
Madelaine, A:
Sorbonne Univ, Grp Hosp Univ La Pitie Salpetriere, INSERM UMR 974, Unite Morphol Neuromusculaire,Inst Myol, F-75013 Paris, France
Fardeau, M:
Sorbonne Univ, Grp Hosp Univ La Pitie Salpetriere, INSERM UMR 974, Unite Morphol Neuromusculaire,Inst Myol, F-75013 Paris, France
Laporte, J:
Univ Strasbourg, CNRS UMR7104, INSERM U1258, Dept Translat Med & Neurogenet,IGBMC, Illkirch Graffenstaden, France
Tizzano, EF:
CIBERER, Barcelona, Spain
Hosp Valle De Hebron, Dept Clin & Mol Genet, Barcelona, Spain
Hosp Valle De Hebron, Rare Dis Div, Barcelona, Spain
Romero, NB:
Sorbonne Univ, Grp Hosp Univ La Pitie Salpetriere, INSERM UMR 974, Unite Morphol Neuromusculaire,Inst Myol, F-75013 Paris, France
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