Mendelian Disorders in an Interstitial Cystitis/Bladder Pain Syndrome Cohort
Abstract Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic pain disorder causing symptoms of urinary frequency, urgency, and bladder discomfort or pain. Although this condition affects a large population, little is known about its etiology. Genetic analyses of whole exome sequencing...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-03-01
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| Series: | Advanced Genetics |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/ggn2.202200013 |
| _version_ | 1811154943196790784 |
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| author | Elicia Estrella Shira Rockowitz Marielle Thorne Pressley Smith Jeanette Petit Veronica Zehnder Richard N. Yu Stuart Bauer Charles Berde Pankaj B. Agrawal Alan H. Beggs Ali G. Gharavi Louis Kunkel Catherine A. Brownstein |
| author_facet | Elicia Estrella Shira Rockowitz Marielle Thorne Pressley Smith Jeanette Petit Veronica Zehnder Richard N. Yu Stuart Bauer Charles Berde Pankaj B. Agrawal Alan H. Beggs Ali G. Gharavi Louis Kunkel Catherine A. Brownstein |
| author_sort | Elicia Estrella |
| collection | DOAJ |
| description | Abstract Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic pain disorder causing symptoms of urinary frequency, urgency, and bladder discomfort or pain. 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 SIX5 variant (ENST00000317578.6:c.472G>A, p.Ala158Thr), consistent with Branchiootorenal syndrome 2 (BOR2). A likely pathogenic heterozygous variant in ATP2A2 (ENST00000539276.2:c.235G>A, p.Glu79Lys) is identified in two unrelated probands, indicating possible Darier‐White disease. Two private heterozygous variants are identified in ATP2C1 (ENST00000393221.4:c.2358A>T, p.Glu786Asp (VUS/Likely Pathogenic) and ENST00000393221.4:c.989C>G, p.Thr330Ser (likely pathogenic)), indicative of Hailey‐Hailey Disease. Sequence kernel association test analysis finds an increased burden of rare ATP2C1 variants in the IC/BPS cases versus a control cohort (p = 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‐based IC/BPS cohort. Conversely, ATP2C1, ATP2A2, and SIX5 may 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. |
| first_indexed | 2024-04-10T04:25:45Z |
| format | Article |
| id | doaj.art-100c09a40bbc4b3d999fc7db393cadf4 |
| institution | Directory Open Access Journal |
| issn | 2641-6573 |
| language | English |
| last_indexed | 2024-04-10T04:25:45Z |
| publishDate | 2023-03-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Genetics |
| spelling | doaj.art-100c09a40bbc4b3d999fc7db393cadf42023-03-10T14:11:58ZengWileyAdvanced Genetics2641-65732023-03-0141n/an/a10.1002/ggn2.202200013Mendelian Disorders in an Interstitial Cystitis/Bladder Pain Syndrome CohortElicia Estrella0Shira Rockowitz1Marielle Thorne2Pressley Smith3Jeanette Petit4Veronica Zehnder5Richard N. Yu6Stuart Bauer7Charles Berde8Pankaj B. Agrawal9Alan H. Beggs10Ali G. Gharavi11Louis Kunkel12Catherine A. Brownstein13Department of Neurology Boston Children's Hospital Harvard Medical School Boston MA 02115 USAThe Manton Center for Orphan disease Research Boston Children's Hospital Harvard Medical School Boston MA 02115 USADivision of Genetics and Genomics Boston Children's Hospital Harvard Medical School Boston MA 02115 USADivision of Genetics and Genomics Boston Children's Hospital Harvard Medical School Boston MA 02115 USADivision of Genetics and Genomics Boston Children's Hospital Harvard Medical School Boston MA 02115 USADivision of Genetics and Genomics Boston Children's Hospital Harvard Medical School Boston MA 02115 USADepartment of Urology Boston Children's Hospital Boston MA 02115 USADepartment of Urology Boston Children's Hospital Boston MA 02115 USAThe Manton Center for Orphan disease Research Boston Children's Hospital Harvard Medical School Boston MA 02115 USADivision of Genetics and Genomics Boston Children's Hospital Harvard Medical School Boston MA 02115 USADivision of Genetics and Genomics Boston Children's Hospital Harvard Medical School Boston MA 02115 USAInstitute for Genomic Medicine Vagelos College of Physicians & Surgeons Columbia University New York NY 10032 USADivision of Genetics and Genomics Boston Children's Hospital Harvard Medical School Boston MA 02115 USADivision of Genetics and Genomics Boston Children's Hospital Harvard Medical School Boston MA 02115 USAAbstract Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic pain disorder causing symptoms of urinary frequency, urgency, and bladder discomfort or pain. 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 SIX5 variant (ENST00000317578.6:c.472G>A, p.Ala158Thr), consistent with Branchiootorenal syndrome 2 (BOR2). A likely pathogenic heterozygous variant in ATP2A2 (ENST00000539276.2:c.235G>A, p.Glu79Lys) is identified in two unrelated probands, indicating possible Darier‐White disease. Two private heterozygous variants are identified in ATP2C1 (ENST00000393221.4:c.2358A>T, p.Glu786Asp (VUS/Likely Pathogenic) and ENST00000393221.4:c.989C>G, p.Thr330Ser (likely pathogenic)), indicative of Hailey‐Hailey Disease. Sequence kernel association test analysis finds an increased burden of rare ATP2C1 variants in the IC/BPS cases versus a control cohort (p = 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‐based IC/BPS cohort. Conversely, ATP2C1, ATP2A2, and SIX5 may 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.https://doi.org/10.1002/ggn2.202200013bladdergeneticsgenitalgenomicsMendelianpain |
| spellingShingle | Elicia Estrella Shira Rockowitz Marielle Thorne Pressley Smith Jeanette Petit Veronica Zehnder Richard N. Yu Stuart Bauer Charles Berde Pankaj B. Agrawal Alan H. Beggs Ali G. Gharavi Louis Kunkel Catherine A. Brownstein Mendelian Disorders in an Interstitial Cystitis/Bladder Pain Syndrome Cohort Advanced Genetics bladder genetics genital genomics Mendelian pain |
| title | Mendelian Disorders in an Interstitial Cystitis/Bladder Pain Syndrome Cohort |
| title_full | Mendelian Disorders in an Interstitial Cystitis/Bladder Pain Syndrome Cohort |
| title_fullStr | Mendelian Disorders in an Interstitial Cystitis/Bladder Pain Syndrome Cohort |
| title_full_unstemmed | Mendelian Disorders in an Interstitial Cystitis/Bladder Pain Syndrome Cohort |
| title_short | Mendelian Disorders in an Interstitial Cystitis/Bladder Pain Syndrome Cohort |
| title_sort | mendelian disorders in an interstitial cystitis bladder pain syndrome cohort |
| topic | bladder genetics genital genomics Mendelian pain |
| url | https://doi.org/10.1002/ggn2.202200013 |
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