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Except for one family, all reported cases have autosomal dominant inheritance and mutations are localized within the three zinc finger (ZNF) DNA\u2010binding domain. The aim of this study was to provide a clinical and molecular analysis of a novel recessive mutation in EGR2.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Clinical and electrophysiological assessments of three affected patients, from a consanguineous family, were performed. Genetic analyses of <jats:italic>EGR2<\/jats:italic> were carried out by Sanger sequencing. Functional effects of clinical recessive mutations were assessed using a mammalian two\u2010hybrid assay.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A novel missense mutation (c.791C&gt;T; p.P264L) in the homozygous state was detected outside the ZNF domains of the <jats:italic>EGR2<\/jats:italic> gene. Three affected siblings presented with distal demyelinating polyneuropathy with severe sensory loss, progressive thoracolumbar scoliosis and trigeminal neuralgia. Respiratory compromise and cranial nerve dysfunction were also found. Our data indicate that the p.P264L mutation prevents interaction of EGR2 transcription factor with NAB corepressors, suggesting that a disruption of the NAB\u2010EGR2 protein interactions can result in dramatic neuropathy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Mutations in, or next to, the R1 domain of EGR2 should be considered with extreme caution for genetic counseling, since these could cause a severe neuropathy with an autosomal recessive manner of transmission.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ene.14512","type":"journal-article","created":{"date-parts":[[2020,9,25]],"date-time":"2020-09-25T16:03:54Z","timestamp":1601049834000},"page":"2662-2667","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Bi\u2010allelic mutations in <i>EGR2<\/i> cause autosomal recessive demyelinating neuropathy by disrupting the EGR2\u2010NAB complex"],"prefix":"10.1111","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3774-9854","authenticated-orcid":false,"given":"V.","family":"Lupo","sequence":"first","affiliation":[{"name":"Unit of Genetics and Genomics of Neuromuscular and Neurodegenerative Disorders Centro de Investigaci\u00f3n Pr\u00edncipe Felipe (CIPF) Valencia Spain"},{"name":"Rare Diseases Joint Units IIS La Fe\u2010CIPF Valencia Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"Won","sequence":"additional","affiliation":[{"name":"Waisman Center University of Wisconsin\u2010Madison Madison WI USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7206-5362","authenticated-orcid":false,"given":"M.","family":"Frasquet","sequence":"additional","affiliation":[{"name":"Neuromuscular Diseases Unit Department of Neurology Hospital Universitari i Polit\u00e8cnic La Fe Valencia Spain"},{"name":"Neuromuscular and Ataxias Research Group Instituto de Investigaci\u00f3n Sanitaria La Fe Valencia Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. 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