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Recessive MYPN mutations cause cap myopathy with occasional nemaline rods
Author(s) -
Lornage Xavière,
Malfatti Edoardo,
Chéraud Chrystel,
Schneider Raphaël,
Biancalana Valérie,
Cuisset JeanMarie,
Garibaldi Matteo,
Eymard Bruno,
Fardeau Michel,
Boland Anne,
Deleuze JeanFrançois,
Thompson Julie,
Carlier RobertYves,
Böhm Johann,
Romero Norma B.,
Laporte Jocelyn
Publication year - 2017
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.24900
Subject(s) - sarcomere , mutation , nemaline myopathy , congenital myopathy , genetics , myopathy , biology , gene , microbiology and biotechnology , myocyte , medicine , pathology , muscle biopsy , biopsy
Congenital myopathies are phenotypically and genetically heterogeneous. We describe homozygous truncating mutations in MYPN in 2 unrelated families with a slowly progressive congenital cap myopathy. MYPN encodes the Z‐line protein myopalladin implicated in sarcomere integrity. Functional experiments demonstrate that the mutations lead to mRNA defects and to a strong reduction in full‐length protein expression. Myopalladin signals accumulate in the caps together with alpha‐actinin. Dominant MYPN mutations were previously reported in cardiomyopathies. Our data uncover that mutations in MYPN cause either a cardiac or a congenital skeletal muscle disorder through different modes of inheritance. Ann Neurol 2017;81:467–473