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Although this condition affects a large population, little is known about its etiology. Genetic analyses of whole exome sequencing are performed on 109 individuals with IC\/BPS. One family has a previously reported\u00a0<jats:italic>SIX5<\/jats:italic>\u00a0variant (ENST00000317578.6:c.472G&gt;A, p.Ala158Thr), consistent with Branchiootorenal syndrome 2 (BOR2). A likely pathogenic heterozygous variant in\u00a0<jats:italic>ATP2A2<\/jats:italic>\u00a0(ENST00000539276.2:c.235G&gt;A, p.Glu79Lys) is identified in two unrelated probands, indicating possible Darier\u2010White disease. Two private heterozygous variants are identified in\u00a0<jats:italic>ATP2C1<\/jats:italic>\u00a0(ENST00000393221.4:c.2358A&gt;T, p.Glu786Asp (VUS\/Likely Pathogenic) and ENST00000393221.4:c.989C&gt;G, p.Thr330Ser (likely pathogenic)), indicative of Hailey\u2010Hailey Disease. Sequence kernel association test analysis finds an increased burden of rare\u00a0<jats:italic>ATP2C1<\/jats:italic>\u00a0variants in the IC\/BPS cases versus a control cohort (<jats:italic>p<\/jats:italic> = 0.03, OR = 6.76), though does not survive Bonferroni correction. The data suggest that some individuals with IC\/BPS may have unrecognized Mendelian syndromes. Comprehensive phenotyping and genotyping aid in understanding the range of diagnoses in the population\u2010based IC\/BPS cohort. Conversely,\u00a0<jats:italic>ATP2C1, ATP2A2<\/jats:italic>,\u00a0and\u00a0<jats:italic>SIX5<\/jats:italic>\u00a0may be candidate genes for IC\/BPS. Further evaluation with larger numbers is needed. Genetically screening individuals with IC\/BPS may help diagnose and treat this painful disorder due to its heterogeneous nature.<\/jats:p>","DOI":"10.1002\/ggn2.202200013","type":"journal-article","created":{"date-parts":[[2022,11,27]],"date-time":"2022-11-27T23:14:34Z","timestamp":1669590874000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Mendelian Disorders in an Interstitial Cystitis\/Bladder Pain Syndrome Cohort"],"prefix":"10.1002","volume":"4","author":[{"given":"Elicia","family":"Estrella","sequence":"first","affiliation":[{"name":"Department of Neurology Boston Children's Hospital Harvard Medical School  Boston MA 02115 USA"},{"name":"Division of Genetics and Genomics Boston Children's Hospital Harvard Medical School  Boston MA 02115 USA"},{"name":"The Manton Center for Orphan disease Research Boston Children's Hospital Harvard Medical School  Boston MA 02115 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shira","family":"Rockowitz","sequence":"additional","affiliation":[{"name":"The Manton Center for Orphan disease Research Boston Children's Hospital Harvard Medical School  Boston MA 02115 USA"},{"name":"Research Computing Information Technology Boston Children's Hospital  Boston MA 02115 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marielle","family":"Thorne","sequence":"additional","affiliation":[{"name":"Division of Genetics and Genomics Boston Children's Hospital Harvard Medical School  Boston MA 02115 USA"},{"name":"The Manton Center for Orphan disease Research Boston Children's Hospital Harvard Medical School  Boston MA 02115 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pressley","family":"Smith","sequence":"additional","affiliation":[{"name":"Division of Genetics and Genomics Boston Children's Hospital Harvard Medical School  Boston MA 02115 USA"},{"name":"The Manton Center for Orphan disease Research Boston Children's Hospital Harvard Medical School  Boston MA 02115 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeanette","family":"Petit","sequence":"additional","affiliation":[{"name":"Division of Genetics and Genomics Boston Children's Hospital Harvard Medical School  Boston MA 02115 USA"},{"name":"The Manton Center for Orphan disease Research Boston Children's Hospital Harvard Medical School  Boston MA 02115 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Veronica","family":"Zehnder","sequence":"additional","affiliation":[{"name":"Division of Genetics and Genomics Boston Children's Hospital Harvard Medical School  Boston MA 02115 USA"},{"name":"The Manton Center for Orphan disease Research Boston Children's Hospital Harvard Medical School  Boston MA 02115 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard N.","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Urology Boston Children's Hospital  Boston MA 02115 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stuart","family":"Bauer","sequence":"additional","affiliation":[{"name":"Department of Urology Boston Children's Hospital  Boston MA 02115 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles","family":"Berde","sequence":"additional","affiliation":[{"name":"The Manton Center for Orphan disease Research Boston Children's Hospital Harvard Medical School  Boston MA 02115 USA"},{"name":"Department of Anesthesiology, Critical Care and Pain Medicine Boston Children's Hospital  Boston MA 02115 USA"},{"name":"Department of Anaesthesia Harvard Medical School  Boston MA 02115 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pankaj B.","family":"Agrawal","sequence":"additional","affiliation":[{"name":"Division of Genetics and Genomics Boston Children's Hospital Harvard Medical School  Boston MA 02115 USA"},{"name":"The Manton Center for Orphan disease Research Boston Children's Hospital Harvard Medical School  Boston MA 02115 USA"},{"name":"Division of Newborn Medicine Boston Children's Hospital Harvard Medical School  Boston MA 02115 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8818-0568","authenticated-orcid":false,"given":"Alan H.","family":"Beggs","sequence":"additional","affiliation":[{"name":"Division of Genetics and Genomics Boston Children's Hospital Harvard Medical School  Boston MA 02115 USA"},{"name":"The Manton Center for Orphan disease Research Boston Children's Hospital Harvard Medical School  Boston MA 02115 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ali G.","family":"Gharavi","sequence":"additional","affiliation":[{"name":"Institute for Genomic Medicine Vagelos College of Physicians &amp; Surgeons Columbia University  New York NY 10032 USA"},{"name":"Division of Nephrology Department of Medicine Vagelos College of Physicians &amp; Surgeons Columbia University  New York NY 10032 USA"},{"name":"Center for Precision Medicine and Genomics Department of Medicine Vagelos College of Physicians &amp; Surgeons Columbia University  New York NY 10032 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Louis","family":"Kunkel","sequence":"additional","affiliation":[{"name":"Division of Genetics and Genomics Boston Children's Hospital Harvard Medical School  Boston MA 02115 USA"},{"name":"The Manton Center for Orphan disease Research Boston Children's Hospital Harvard Medical School  Boston MA 02115 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7371-0340","authenticated-orcid":false,"given":"Catherine A.","family":"Brownstein","sequence":"additional","affiliation":[{"name":"Division of Genetics and Genomics Boston Children's Hospital Harvard Medical School  Boston MA 02115 USA"},{"name":"The Manton Center for Orphan disease Research Boston Children's Hospital Harvard Medical School  Boston MA 02115 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,11,27]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.ju.0000146114.53828.82"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2011.03.132"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2012.08.088"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.genhosppsych.2011.01.004"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00192-008-0712-x"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00192-013-2057-3"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2007.01.124"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1806891"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.7326\/M17-1319"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2012.10.007"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1214479"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI95300"},{"key":"e_1_2_9_13_1","first-page":"E581","volume":"19","author":"Jhang J. 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