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The core clinical phenotype comprises a characteristic facial gestalt, marked developmental delay, and myopia. Additional, nonobligatory features include obesity, microcephaly, short stature, muscular hypotonia, scoliosis, narrow hands and feet, progressive retinopathy, as well as neutropenia. Here we report a novel homozygous nonsense mutation in the <jats:italic>VPS13B<\/jats:italic> gene and previously undescribed clinical features in a 19\u2010year\u2010old woman with developmental delay, intellectual disability, and a particular facial appearance. The patient showed several features consistent with CS. In addition, the parents observed congenital alacrima and anhidrosis persisting until onset of puberty. The diagnosis was not established based on the clinical phenotype. We performed whole\u2010genome sequencing and identified a novel homozygous nonsense mutation c.62T&gt;G (NM_152564.4), p.(Leu21*) in the <jats:italic>VPS13B<\/jats:italic> gene. Our findings extended the previously reported phenotype of CS. We conclude that transient, prepubertal alacrima and anhidrosis are part of the phenotypic spectrum of CS associated with a novel homozygous nonsense mutation in the <jats:italic>VPS13B<\/jats:italic> gene.<\/jats:p>","DOI":"10.1002\/ajmg.a.61435","type":"journal-article","created":{"date-parts":[[2019,12,11]],"date-time":"2019-12-11T12:27:48Z","timestamp":1576067268000},"page":"570-575","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["A novel homozygous nonsense mutation of <i>VPS13B<\/i> associated with previously unreported features of Cohen syndrome"],"prefix":"10.1002","volume":"182","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9407-1410","authenticated-orcid":false,"given":"Katrin","family":"Koehler","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Medizinische Fakult\u00e4t Technische Universit\u00e4t Dresden  Dresden Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Schuelke","sequence":"additional","affiliation":[{"name":"Department of Neuropediatrics and NeuroCure Clinical Research Center Charit\u00e9\u2010Universit\u00e4tsmedizin Berlin  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna K.","family":"Hell","sequence":"additional","affiliation":[{"name":"Pediatric Orthopaedics; Department of Trauma, Orthopaedic and Plastic Surgery University Medical Center G\u00f6ttingen  G\u00f6ttingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Schittkowski","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Section for Strabismus, Neuroophthalmology and Oculoplastics University Medical Center G\u00f6ttingen  G\u00f6ttingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Huebner","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Medizinische Fakult\u00e4t Technische Universit\u00e4t Dresden  Dresden Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Knut","family":"Brockmann","sequence":"additional","affiliation":[{"name":"Interdisciplinary Pediatric Center for Children with Developmental Disabilities and Severe Chronic Disorders University Medical Center G\u00f6ttingen  G\u00f6ttingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,12,11]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.32239"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.40.4.233"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(73)80493-7"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2011.01669.x"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2014.22"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.30033"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1136\/adc.64.7.1080"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1086\/422219"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/1096-8628(20010801)102:2<125::AID-AJMG1439>3.0.CO;2-0"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2013.08.002"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1086\/375454"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320370126"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature19057"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2008.273"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1097\/MCD.0b013e3282742530"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/ceo.12391"},{"issue":"9","key":"e_1_2_9_18_1","first-page":"e3330","article-title":"Cohen syndrome: Review of the literature","volume":"10","author":"Rodrigues J. 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