{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T17:56:09Z","timestamp":1785520569594,"version":"3.56.0"},"reference-count":56,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2024,4,22]],"date-time":"2024-04-22T00:00:00Z","timestamp":1713744000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","award":["2018\u2013\u201002487"],"award-info":[{"award-number":["2018\u2013\u201002487"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01MH110427"],"award-info":[{"award-number":["R01MH110427"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt B"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Individuals with severe and treatment\u2010resistant obsessive\u2010compulsive disorder (trOCD) represent a small but severely disabled group of patients. Since trOCD cases eligible for deep brain stimulation (DBS) probably comprise the most severe end of the OCD spectrum, we hypothesize that they may be more likely to have a strong genetic contribution to their disorder. Therefore, while the worldwide population of DBS\u2010treated cases may be small (~300), screening these individuals with modern genomic methods may accelerate gene discovery in OCD. As such, we have begun to collect DNA from trOCD cases who qualify for DBS, and here we report results from whole exome sequencing and microarray genotyping of our first five cases. All participants had previously received DBS in the bed nucleus of stria terminalis (BNST), with two patients responding to the surgery and one showing a partial response. Our analyses focused on gene\u2010disruptive rare variants (GDRVs; rare, predicted\u2010deleterious single\u2010nucleotide variants or copy number variants overlapping protein\u2010coding genes). Three of the five cases carried a GDRV, including a missense variant in the ion transporter domain of\n                    <jats:italic>KCNB1<\/jats:italic>\n                    , a deletion at 15q11.2, and a duplication at 15q26.1. The\n                    <jats:italic>KCNB1<\/jats:italic>\n                    variant (hg19 chr20\u201047991077\u2010C\u2010T, NM_004975.3:c.1020G&gt;A, p.Met340Ile) causes substitution of methionine for isoleucine in the trans\u2010membrane region of neuronal potassium voltage\u2010gated ion channel KV2.1. This\n                    <jats:italic>KCNB1<\/jats:italic>\n                    substitution (Met340Ile) is located in a highly constrained region of the protein where other rare missense variants have previously been associated with neurodevelopmental disorders. The patient carrying the Met340Ile variant responded to DBS, which suggests that genetic factors could potentially be predictors of treatment response in DBS for OCD. In sum, we have established a protocol for recruiting and genomically characterizing trOCD cases. Preliminary results suggest that this will be an informative strategy for finding risk genes in OCD.\n                  <\/jats:p>","DOI":"10.1002\/ajmg.b.32983","type":"journal-article","created":{"date-parts":[[2024,4,23]],"date-time":"2024-04-23T00:05:35Z","timestamp":1713830735000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Genomics of severe and treatment\u2010resistant obsessive\u2013compulsive disorder treated with deep brain stimulation: A preliminary investigation"],"prefix":"10.1002","volume":"195","author":[{"given":"Long Long","family":"Chen","sequence":"first","affiliation":[{"name":"Centre for Psychiatry Research, Department of Clinical Neuroscience Karolinska Institutet &amp; Stockholm Health Care Services  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matilda","family":"Naesstr\u00f6m","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences\/Psychiatry Ume\u00e5 University  Ume\u00e5 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Halvorsen","sequence":"additional","affiliation":[{"name":"Centre for Psychiatry Research, Department of Clinical Neuroscience Karolinska Institutet &amp; Stockholm Health Care Services  Stockholm Sweden"},{"name":"Department of Genetics University of North Carolina at Chapel Hill  Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anders","family":"Fytagoridis","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Karolinska Institutet and University Hospital  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie B.","family":"Crowley","sequence":"additional","affiliation":[{"name":"Independent researcher  Chapel Hill North Carolina 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North Carolina at Chapel Hill  Chapel Hill North Carolina USA"},{"name":"Department of Psychiatry University of North Carolina at Chapel Hill  Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Pascal","sequence":"additional","affiliation":[{"name":"Centre for Psychiatry Research, Department of Clinical Neuroscience Karolinska Institutet &amp; Stockholm Health Care Services  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,4,22]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.23915"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.16679"},{"key":"e_1_2_10_4_1","first-page":"28","article-title":"The clinical global impressions scale: Applying a research tool in clinical practice","volume":"4","author":"Busner 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