A TOR1AIP1 variant segregating with an early onset limb girdle myasthenia-Support for the role of LAP1 in NMJ function and disease

Edoardo Malfatti; Tara Catchpool; Sonia Nouioua; Hellal Sihem; Emmanuel Fournier; Robert Y Carlier; Nastasia Cardone; Mark R Davis; Nigel G Laing; Damien Sternberg; Gianina Ravenscroft

doi:10.1111/nan.12743

A TOR1AIP1 variant segregating with an early onset limb girdle myasthenia-Support for the role of LAP1 in NMJ function and disease

Neuropathol Appl Neurobiol. 2022 Feb;48(1):e12743. doi: 10.1111/nan.12743. Epub 2021 Jul 13.

Authors

Edoardo Malfatti^{1

2}, Tara Catchpool³, Sonia Nouioua^{4

5}, Hellal Sihem^{5

6}, Emmanuel Fournier⁷, Robert Y Carlier⁸, Nastasia Cardone^{1

9

10}, Mark R Davis^{11

12}, Nigel G Laing³, Damien Sternberg¹³, Gianina Ravenscroft^{3

12}

Affiliations

¹ APHP, North-East-Ile-de-France Neuromuscular Pathology Reference Center, Henri-Mondor University Hospital, Paris, France.
² UVSQ-INSERM Neuromuscular Handicap: Applied Physiology, Biotherapy and Pharmacology, UFR Simone Veil-Santé, Versailles Saint-Quentin-en-Yvelines University, Paris, France.
³ Harry Perkins Institute of Medical Research, Centre of Medical Research, University of Western Australia, Nedlands, Western Australia, Australia.
⁴ Department of Neurology of the EHS of Cherchell, University Centre of Tipaza, Tipaza, Algeria.
⁵ NeuroSciences Research Laboratory, University of Algiers Benyoucef Benkhedda, Alger, Algeria.
⁶ Central Laboratory of Biochemistry, CHU Mustapha, Algiers, Algeria.
⁷ APHP, Department of Neurophysiology, GH Pitié-Salpêtrière, Sorbonne University, Paris, France.
⁸ APHP, DMU Smart Imaging, Medical imaging Department, Raymond Poincaré Teaching Hospital, North-East-Ile-de-France Neuromuscular Pathology Reference Center, GH University Paris-Saclay, Paris, France.
⁹ Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy.
¹⁰ Department of Neuroscience, Psychology, Drug Research and Child Health, University of Florence, Florence, Italy.
¹¹ PathWest Diagnostic Genomics, Nedlands, Western Australia, Australia.
¹² School of Biomedical Sciences, University of Western Australia, Nedlands, Western Australia, Australia.
¹³ APHP, Metabolic Biochemistry Department, Genetics Center, Pitié-Salpêtrière Hospital Group, Center of Research in Myology, APHP Sorbonne University, Paris, France.

PMID: 34164833
DOI: 10.1111/nan.12743

Abstract

Rare pathogenic variants in TOR1AIP1 (OMIM 614512), coding the inner nuclear membrane protein lamin-associated protein 1 (LAP1), have been associated with a spectrum of disorders including limb girdle muscular dystrophy with cardiac involvement and a severe multisystem phenotype. Recently, Cossins et al reported two siblings with limb girdle muscular dystrophy and impaired transmission of the neuromuscular synapse, demonstrating that defective LAP1 may lead to a congenital myasthenic syndrome. Herein, we describe the association of TOR1AIP1 deficiency with congenital myasthenic syndrome in three siblings.

Keywords: CMS; LAP1; TOR1AIP1; myasthenic syndrome; nuclear envelop.

Publication types

Case Reports
Research Support, Non-U.S. Gov't

MeSH terms

Cytoskeletal Proteins / genetics
Humans
Lamins / genetics
Membrane Proteins / genetics
Muscular Dystrophies, Limb-Girdle* / genetics
Mutation
Myasthenic Syndromes, Congenital* / genetics
Phenotype

Substances

Cytoskeletal Proteins
Lamins
Membrane Proteins
TOR1AIP1 protein, human