Narcolepsy type 1 (NT1) is a rare and chronic neurological disease characterized by sudden sleep attacks, overwhelming daytime drowsiness, and cataplexy. To contribute to the understanding of NT1 genetic causes, here we describe a whole-genome analysis of a monozygotic twin pair discordant for NT1. Our study revealed that although both twins have the same pathogenic mutations in NT1 associated genes (such as HLA-DQB1*06:02:01, HLA-DRB1*11:01:02/*15:03:01) the unaffected twin has mutations in genes outside the HLA loci that could be suppressing the NT1 phenotype. These results support the notion that NT1 has an immunological basis but that protective mutations in non-HLA might interfere with the clinical manifestation of the disease.

中文翻译：

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1型发作性睡病不一致的单卵双胞胎的全基因组分析

发作性睡病 1 型 (NT1) 是一种罕见的慢性神经系统疾病，其特征是突然睡眠发作、白天过度嗜睡和猝倒。为了有助于理解 NT1 的遗传原因，我们在这里描述了对 NT1 不一致的单卵双胞胎的全基因组分析。我们的研究表明，虽然双胞胎在 NT1 相关基因（如 HLA-DQB1*06:02:01、HLA-DRB1*11:01:02/*15:03:01）中具有相同的致病突变，但未受影响的双胞胎具有HLA 基因座外的基因突变可能会抑制 NT1 表型。这些结果支持 NT1 具有免疫学基础但非 HLA 中的保护性突变可能会干扰该疾病的临床表现的观点。