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We report here a severe defect of neuromuscular transmission in a consanguineous patient with a homozygous variant in the laminin alpha\u20105 subunit gene (<jats:italic>LAMA5)<\/jats:italic>. The variant c.8046C&gt;T (p.Arg2659Trp) is rare and has a predicted deleterious effect. The affected individual, who also carries a rare homozygous sequence variant in <jats:italic>LAMA1<\/jats:italic>, had muscle weakness, myopia, and facial tics. Magnetic resonance imaging of brain showed mild volume loss and periventricular T2 prolongation. Repetitive nerve stimulation revealed 50% decrement of compound muscle action potential amplitudes and 250% facilitation immediately after exercise, Endplate studies identified a profound reduction of the endplate potential quantal content and endplates with normal postsynaptic folding that were denuded or partially occupied by small nerve terminals. Expression studies revealed that p.Arg2659Trp caused decreased binding of laminin alpha\u20105 to SV2A and impaired laminin\u2010521 cell\u2010adhesion and cell projection support in primary neuronal cultures. In summary, this report describing severe neuromuscular transmission failure in a patient with a <jats:italic>LAMA5<\/jats:italic> mutation expands the list of phenotypes associated with defects in genes encoding alpha\u2010laminins.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.38291","type":"journal-article","created":{"date-parts":[[2017,5,25]],"date-time":"2017-05-25T17:23:22Z","timestamp":1495733002000},"page":"2240-2245","source":"Crossref","is-referenced-by-count":38,"title":["Presynaptic congenital myasthenic syndrome with a homozygous sequence variant in <i>LAMA5<\/i> combines myopia, facial tics, and failure of neuromuscular transmission"],"prefix":"10.1002","volume":"173","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0918-0760","authenticated-orcid":false,"given":"Ricardo A.","family":"Maselli","sequence":"first","affiliation":[{"name":"Department of Neurology University of California Davis Sacramento 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