Mendelian Disorders in an Interstitial Cystitis/Bladder Pain Syndrome Cohort.
Mendelian Disorders in an Interstitial Cystitis/Bladder Pain Syndrome Cohort.
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DOI：
10.1002/ggn2.202200013
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发表时间：
2023-03
期刊：
影响因子：
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通讯作者：
Brownstein, Catherine A
中科院分区：
文献类型：
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作者：
Estrella, Elicia;Rockowitz, Shira;Thorne, Marielle;Smith, Pressley;Petit, Jeanette;Zehnder, Veronica;Yu, Richard N;Bauer, Stuart;Berde, Charles;Agrawal, Pankaj B;Beggs, Alan H;Gharavi, Ali G;Kunkel, Louis;Brownstein, Catherine A
间质性膀胱炎/膀胱疼痛综合征（IC/BPS）是一种慢性疼痛疾病，可引起尿频、尿急和膀胱不适或疼痛症状。虽然这种情况影响了大量人口，但对其病因知之甚少。对109例IC/BPS患者进行全外显子组测序的遗传分析。一个家族具有先前报道的SIX 5变体（ENST 00000317578.6：c.472G>A，p.Ala158Thr），与鳃卵巢肾综合征2（BOR 2）一致。在两个不相关的先证者中鉴定出ATP 2A 2中可能的致病性杂合变体（ENST 00000539276.2：c.235G>A，p.Glu79Lys），表明可能存在Darier白色病。在ATP 2C 1中鉴定出两种私有杂合变体（ENST 00000393221.4：c.2358A>T，p.Glu786Asp（VUS/可能致病）和ENST 00000393221.4：c.989C>G，p.Thr330Ser（可能致病）），表明Hailey-Hailey病。序列核关联检验分析发现IC/BPS病例中罕见ATP 2C 1变异体的负担相对于对照组增加（p = 0.03，OR = 6.76），尽管不能在Bonferroni校正后存活。这些数据表明，一些IC/BPS患者可能患有未被识别的孟德尔综合征。综合表型和基因分型有助于了解基于人群的IC/BPS队列的诊断范围。相反，ATP 2C 1、ATP 2A 2和SIX 5可能是IC/BPS的候选基因。需要对更多的数字进行进一步评价。遗传筛查个体与IC/BPS可能有助于诊断和治疗这种痛苦的疾病，由于其异质性。对109名患有间质性膀胱炎/膀胱疼痛综合征的个体的外显子组数据进行孟德尔疾病分析。在队列中鉴定的两个基因，ATP 2C 1和ATP 2A 2，与皮肤表型相关。需要更多的进一步评估，尽管遗传筛查IC/BPS个体可能有助于诊断和治疗这种疼痛性疾病，因为它的异质性。
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. Exome data for 109 individuals with interstitial cystitis/bladder pain syndrome is analyzed for Mendelian disorders. Two genes identified within the cohort, ATP2C1 and ATP2A2, are associated with dermatological phenotypes. Further evaluation with larger numbers is needed, though genetically screening individuals with IC/BPS may be useful in diagnosing and treating this painful disorder due to its heterogeneous nature.