Kadhi Ayat, Hamie Lamiaa, Eid Edward, Nemer Georges, Kurban Mazen
Division of Genomics and Translational Biomedicine, College of Health and Life Sciences, Hamad Bin Khalifa University, Doha, Qatar.
College of Health and Sciences, University of Doha for Science and Technology, Doha, Qatar.
Dermatol Pract Concept. 2025 Jan 30;15(1):4935. doi: 10.5826/dpc.1501a4935.
Genodermatoses refer to a group of heterogenous rare genetic diseases with cutaneous expression. Several genodermatoses present with multisystem involvement that can range from mild to life-threatening conditions leading to increased morbidity and mortality.
Given the paucity in the literature in the field of genodermatoses, especially in the Middle East and North Africa (MENA) region, and building upon the first established genodermatoses database based in Lebanon, this study aimed to decipher the genetic basis of two different types of skin-inherited diseases (androgenic alopecia and vitiligo).
We conducted a pilot study on two subjects with androgenic alopecia and vitiligo to investigate the possibility of a digenic inheritance model as a potential underlying mechanism for these conditions. Whole exome sequencing (WES) and Gene Expression Omnibus (GEO) DataSets were employed to validate the methodology and provide a foundation for future, larger-scale studies.
We identified two gene variants FOXC1(p.His484Tyr) and SMARCD1 (p.Arg351Cys) responsible for androgenic alopecia and HPS1(p.Ser566Ter) and ITK (p.Pro521Leu) responsible for vitiligo. Further analysis using GEO DataSets confirmed the association between the genes involved in each each disease.
This study identified novel candidate disease genes and inheritance model that could explain the underlying phenotypes that could open the door for a better-guided genomic approach for personalized treatment and early diagnosis.
遗传性皮肤病是一组具有皮肤表现的异质性罕见遗传病。几种遗传性皮肤病会出现多系统受累，范围从轻度到危及生命的情况，导致发病率和死亡率增加。
鉴于遗传性皮肤病领域，特别是中东和北非（MENA）地区的文献匮乏，并且基于黎巴嫩建立的首个遗传性皮肤病数据库，本研究旨在破译两种不同类型皮肤遗传病（雄激素性脱发和白癜风）的遗传基础。
我们对两名患有雄激素性脱发和白癜风的受试者进行了一项试点研究，以调查双基因遗传模式作为这些病症潜在潜在机制的可能性。采用全外显子组测序（WES）和基因表达综合数据库（GEO）数据集来验证该方法，并为未来更大规模的研究提供基础。
我们鉴定出两个导致雄激素性脱发的基因变异FOXC1（p.His484Tyr）和SMARCD1（p.Arg351Cys），以及两个导致白癜风的基因变异HPS1（p.Ser566Ter）和ITK（p.Pro521Leu）。使用GEO数据集进行的进一步分析证实了每种疾病所涉及基因之间的关联。
本研究鉴定出了新的候选疾病基因和遗传模式，它们可以解释潜在的表型，这可能为更好地指导个性化治疗和早期诊断的基因组方法打开大门。
