Gaikwad Pallavi, Bargir Umair A, Jodhawat Neha, Dalvi Aparna, Shinde Shweta, Tamhankar Parag, Setia Priyanka, Kambli Priyanka, Dhawale Amruta, Temkar Lavina, Vedpathak Disha, Jose Amrutha, Gupta Maya, Yadav-Malik Reetika, Dutta Shubhankar, Bose Kokoli, Taur Prasad, Gowri Vijaya, Iyengar Vaishnavi, Chougule Akshaya, Desai Mukesh, Sivasankaran Meena, Bhattad Sagar, Balaji Sarath, Mudaliar Sangeeta, Kacha Ashruti, Subramanian Girish, Patel Swati, Sharma Sujata, Sampagar Abhilasha, Madkaikar Manisha
Indian Council of Medical Research (ICMR)-National Institute of Immunohaematology (NIIH), Parel, Mumbai, India.
Centre for Medical Genetics, Mulund, Mumbai, India.
J Clin Immunol. 2024 Dec 17;45(1):56. doi: 10.1007/s10875-024-01848-w.
Wiskott-Aldrich syndrome (WAS) is an X-linked genetic disorder characterized by distinctive features including microthrombocytopenia, eczema and recurrent infections. In the present study we report clinical, immunological and molecular spectrum of 41 WAS patients diagnosed over last five years.
Clinical and family history was collected from case records. Comprehensive immunological assessments including lymphocyte subset analysis, and flow cytometry based evaluation of WAS protein (WASP) expressions were performed in patients along with evaluation of carrier status in mothers. Genetic analysis was carried out with either Sanger sequencing or targeted exome sequencing.
The patients included in this study presented at a median age of 9.5 months, with two adult cases. Clinical manifestations encompassed thrombocytopenia, eczema, bleeding, diarrhea, respiratory tract infections, CMV infection, and malignancy. Immunological phenotype revealed T cell lymphopenia, B cell lymphopenia, and elevated IgE levels. Flow cytometry analysis of WASP was performed in 36 cases out of which 68.42% demonstrated complete absent expression while others showed reduced expression. Genetic analysis highlighted that the majority of mutations affect the WH1 domain of WASP while both adult patients showed intronic mutations. Molecular Dynamics analysis conducted for the novel variants P398R and G33R showed an average RMSD (Å) higher than that of the wild type, indicating greater structural perturbations in WASP.
In the present study we have documented 56.09% novel WAS mutations in Indian cohort. Notably, the application of flow cytometry has emerged as a valuable and efficient diagnostic tool for identifying these WAS patients.
威斯科特-奥尔德里奇综合征（WAS）是一种X连锁遗传病，其特征包括微血小板减少、湿疹和反复感染。在本研究中，我们报告了过去五年中确诊的41例WAS患者的临床、免疫和分子谱。
从病例记录中收集临床和家族史。对患者进行全面的免疫评估，包括淋巴细胞亚群分析和基于流式细胞术的威斯科特-奥尔德里奇综合征蛋白（WASP）表达评估，同时评估母亲的携带者状态。采用桑格测序或靶向外显子组测序进行基因分析。
本研究纳入的患者中位年龄为9.5个月，有两例成年病例。临床表现包括血小板减少、湿疹、出血、腹泻、呼吸道感染、巨细胞病毒感染和恶性肿瘤。免疫表型显示T细胞淋巴细胞减少、B细胞淋巴细胞减少和IgE水平升高。对36例患者进行了WASP的流式细胞术分析，其中68.42%显示完全不表达，其他患者显示表达降低。基因分析突出显示，大多数突变影响WASP的WH1结构域，而两名成年患者均显示内含子突变。对新变体P398R和G33R进行的分子动力学分析显示，平均均方根偏差（Å）高于野生型，表明WASP的结构扰动更大。
在本研究中，我们记录了印度队列中56.09%的新型WAS突变。值得注意的是，流式细胞术的应用已成为识别这些WAS患者的一种有价值且高效的诊断工具。
