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Despite this, there is limited knowledge of the clinical and genetic spectrum of disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We leverage the diagnostic utility of exome and genome sequencing and describe novel biallelic variants in <jats:italic>PLEKHG5<\/jats:italic> in 13 individuals from nine unrelated families originating from four different countries. We compare our phenotypic and genotypic findings with a comprehensive review of cases previously described in the literature.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found that patients presented with variable disease severity at different ages of onset (8\u201325\u00a0years). In our cases, weakness usually started proximally, progressing distally, and can be associated with intermediate slow conduction velocities and minor clinical sensory involvement. We report three novel nonsense and four novel missense pathogenic variants associated with these <jats:italic>PLEKHG5<\/jats:italic>\u2010associated neuropathies, which are phenotypically spinal muscular atrophy (SMA) or intermediate Charcot\u2010Marie\u2010Tooth disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p><jats:italic>PLEKHG5<\/jats:italic>\u2010associated neuropathies should be considered as an important differential in non\u20105q SMAs even in the presence of mild sensory impairment and a candidate causative gene for a wide range of hereditary neuropathies. We present this series of cases to further the understanding of the phenotypic and molecular spectrum of <jats:italic>PLEKHG5<\/jats:italic>\u2010associated diseases.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ene.14649","type":"journal-article","created":{"date-parts":[[2020,11,21]],"date-time":"2020-11-21T18:27:43Z","timestamp":1605983263000},"page":"1344-1355","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Novel variants broaden the phenotypic spectrum of <i>PLEKHG5<\/i>\u2010associated neuropathies"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6668-7202","authenticated-orcid":false,"given":"Zhongbo","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Neurodegenerative Disease University College London Queen Square Institute of Neurology University College London London UK"},{"name":"Department of Neuromuscular Disease University College London Queen Square Institute of Neurology University College London London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Reza","family":"Maroofian","sequence":"additional","affiliation":[{"name":"Department of Neuromuscular Disease University College London Queen Square Institute of Neurology University College London London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A. Nazl\u0131","family":"Ba\u015fak","sequence":"additional","affiliation":[{"name":"School of Medicine Neurodegeneration Research Laboratory KUTTAM\u2010NDAL Ko\u00e7 University Istanbul Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8596-1120","authenticated-orcid":false,"given":"Leena","family":"Shingavi","sequence":"additional","affiliation":[{"name":"Department of Neurology National Institute of Mental Health and Neurosciences (NIMHANS) Bengaluru India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mert","family":"Karakaya","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics Center for Molecular Medicine and Center for Rare Diseases University Hospital Cologne University of Cologne Cologne Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephanie","family":"Efthymiou","sequence":"additional","affiliation":[{"name":"Department of Neuromuscular Disease University 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