Theut Riis P, Loft I C, Yazdanyar S, Kjaersgaard Andersen R, Pedersen O B, Ring H C, Huber R, Sultan M, Loesche C, Saunte D M L, Jemec G B E
Department of Dermatology, Zealand University Hospital, Roskilde, Denmark.
Department of Clinical Immunology, Naestved Hospital, Naestved, Denmark.
J Eur Acad Dermatol Venereol. 2021 May;35(5):1203-1211. doi: 10.1111/jdv.17095. Epub 2021 Mar 3.
Hidradenitis suppurativa (HS) is not a well-studied or easily treated disease. Genetic information is essential for advances in the understanding and treatment of HS. This study aims to examine mutations in the gamma-secretase complex, the Notch signalling pathway and to perform a Mendelian analysis of genetic variants that segregated with disease in a full exome sequencing of 11 families with HS.
Whole-exome sequencing and Mendelian analysis of 11 families with HS from Denmark. Patients with a clinical diagnosis of active HS and a positive family history of HS were recruited. Consenting family members were enrolled and examined for HS as well. We included 11 families, with a total of 51 participants, 24 with HS and 27 without. Whole-exome sequencing using HiSeq platform as paired-end 2 × 150 bases was used.
We found mutations in the Notch pathway for all families. We found mutations in the PSENEN and APH1B of the gamma-secretase genes. We also report 161 variants of unknown significance that segregated with the disease within these families.
We did not find causative mutation for each family in this study, supporting the theory that HS is rarely caused by single-gene mutations. We suggest that future genetic studies should be focused on genome-wide association with thousands of cases, as this technique is better suited for suspected polygenic diseases.
化脓性汗腺炎（HS）是一种研究较少且难以治疗的疾病。遗传信息对于深入了解和治疗HS至关重要。本研究旨在检测γ-分泌酶复合物、Notch信号通路中的突变，并对11个HS家族的全外显子测序中与疾病相关的遗传变异进行孟德尔分析。
对来自丹麦的11个HS家族进行全外显子测序和孟德尔分析。招募临床诊断为活动性HS且有HS家族史阳性的患者。同意参与的家庭成员也被纳入并接受HS检查。我们纳入了11个家族，共51名参与者，其中24名患有HS，27名未患HS。使用HiSeq平台进行全外显子测序，测序方式为双端2×150碱基。
我们在所有家族中均发现了Notch通路中的突变。我们在γ-分泌酶基因的PSENEN和APH1B中发现了突变。我们还报告了161个在这些家族中与疾病相关的意义未明的变异。
在本研究中，我们未找到每个家族的致病突变，这支持了HS很少由单基因突变引起的理论。我们建议未来的遗传研究应聚焦于对数千例病例的全基因组关联研究，因为该技术更适合疑似多基因疾病。
