Griscelli syndrome type 2 (GS2) is a rare autosomal recessive disorder caused by pathogenic variants in the RAB27A gene and characterized by partial albinism, immunodeficiency, and occasional hematological and neurological involvement. We reviewed and analyzed the medical records of 12 individuals with GS2 from six families belonging to a highly consanguineous Qatari tribe and with a recurrent pathogenic variant in the RAB27A gene (NM_004580.4: c.244C > T, p.Arg82Cys). Detailed demographic, clinical, and molecular data were collected. Cutaneous manifestations were the most common presentation (42%), followed by neurological abnormalities (33%) and immunodeficiency (25%). The most severe manifestation was HLH (33%). Among the 12 patients, three patients (25%) underwent HSCT, and four (33%) died. The cause of death in all four patients was deemed HLH, providing evidence for this complication's fatal nature. Interestingly, two affected patients (16%) were asymptomatic. This report highlights the broad spectrum of clinical presentations of GS2 associated with a founder variant in the RAB27A gene (c.244C > T, p.Arg82Cys). Early suspicion of GS2 among Qatari patients with cutaneous manifestations, neurological findings, immunodeficiency, and HLH would shorten the diagnostic odyssey, guide early and appropriate treatment, and prevent fatal outcomes.

中文翻译：

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创始人RAB27A变体在卡塔尔家庭中导致2型格里切利综合征的表型异质性。

Griscelli综合征2型（GS2）是由RAB27A中的致病变异引起的罕见常染色体隐性遗传疾病该基因的特征是部分白化病，免疫缺陷以及偶尔的血液和神经系统疾病。我们回顾并分析了来自六个血统的卡塔尔部落的六个家族的12例GS2的患者的病历，这些患者的RAB27A基因具有复发性致病变异（NM_004580.4：c.244C> T，p.Arg82Cys）。收集了详细的人口统计，临床和分子数据。皮肤表现是最常见的表现（42％），其次是神经系统异常（33％）和免疫缺陷（25％）。最严重的表现是HLH（33％）。在这12例患者中，有3例（25％）接受了HSCT，有4例（33％）死亡。所有四名患者的死亡原因均被认为是HLH，为这种并发症的致命性提供了证据。有趣的是 两名受影响的患者（16％）无症状。本报告重点介绍了与GS2中的创始者变体相关的GS2临床表现的广泛领域。RAB27A基因（c.244C> T，p.Arg82Cys）。在具有皮肤表现，神经系统发现，免疫缺陷和HLH的卡塔尔患者中，早期怀疑GS2会缩短诊断过程，指导早期和适当的治疗，并防止致命的后果。