Metpally Raghu P, Vishweswaraiah Sangeetha, Krishnamurthy Sarathbabu, Saiyed Nazia, Stahl Richard C, Golden Alicia, Denisenko Andrew, Staples Jeffrey, Gonzaga-Jauregui Claudia, Carey David J, Bechara Falk, Jemec Gregor B E, Williams Heinric, Radhakrishna Uppala
Department of Molecular and Functional Genomics, Geisinger, Danville, Pennsylvania, USA.
Department of Obstetrics and Gynecology, Corewell Health William Beaumont University Hospital, Royal Oak, Michigan, USA.
Dermatology. 2024;240(5-6):739-749. doi: 10.1159/000540359. Epub 2024 Oct 11.
Hidradenitis suppurativa (HS) is a prevalent and persistent inflammatory skin disorder, lacking a known cure or effective biomarkers for early diagnosis at present. The genetic determinants of HS have not been fully documented, but it is believed to result from a combination of genetic and environmental factors.
To identify relevant HS gene variants in sporadic HS patients, this study utilized longitudinal electronic health records (EHRs) and whole-exome sequencing. DNA exome sequencing data from 92,455 participant samples in the MyCode biobank, linked to Geisinger's EHR, were analyzed. This cohort included 1,092 HS cases and 91,363 healthy controls. The MyCode EHR has a median longitudinal follow-up of 15 years per participant, with an average of 87 clinical encounters, 687 laboratory tests, and 7 procedures.
There were 1,092 (901 females and 191 males) participants aged 14-89 years (median 47 years) with HS (L73.2), indicating a 1.18% prevalence and accounting for a 4.7:1 female-to-male ratio among the individuals presenting for clinical care. γ-secretase complex, syndromic, and autoinflammatory gene variants were assessed. Potential pathogenic variants were identified among 66 individuals in the HS genes studied. Molecularly, the estimated HS variant prevalence was 1:1,400 in the cohort, 12.3% of variant carriers had HS diagnosis in EHR.
Using longitudinal EHR data, genomic screening identified HS-associated gene variants in a defined group of sporadic HS patients to augment the clinical diagnosis, particularly in cases of ambiguity. Based on this study, the field of skin disorders can benefit from a personalized approach to HS diagnosis using large-scale sequencing.
化脓性汗腺炎（HS）是一种常见且持续存在的炎症性皮肤病，目前尚无已知的治愈方法或用于早期诊断的有效生物标志物。HS的遗传决定因素尚未完全明确，但据信是遗传和环境因素共同作用的结果。
为了在散发性HS患者中鉴定相关的HS基因变异，本研究利用了纵向电子健康记录（EHR）和全外显子测序。分析了来自MyCode生物样本库中92455个参与者样本的DNA外显子测序数据，这些数据与Geisinger的EHR相关联。该队列包括1092例HS病例和91363例健康对照。MyCode EHR对每位参与者的纵向随访中位数为15年，平均有87次临床会诊、687次实验室检查和7项操作。
有1092名（901名女性和191名男性）年龄在14 - 89岁（中位数47岁）的参与者患有HS（L73.2），患病率为1.18%，在接受临床护理的个体中女性与男性的比例为4.7:1。评估了γ-分泌酶复合物、综合征性和自身炎症性基因变异。在所研究的HS基因中，66名个体中鉴定出潜在的致病变异。从分子层面来看，该队列中HS变异的估计患病率为1:1400，12.3%的变异携带者在EHR中有HS诊断。
利用纵向EHR数据，基因组筛查在一组明确的散发性HS患者中鉴定出与HS相关的基因变异，以加强临床诊断，特别是在诊断不明确的情况下。基于本研究，皮肤病领域可受益于使用大规模测序对HS进行个性化诊断的方法。
