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. 2024 Dec 17;45(1):56.
doi: 10.1007/s10875-024-01848-w.

Mutational Landscape of Patients with Wiskott Aldrich Syndrome: Update from India

Pallavi Gaikwad  1 , Umair A Bargir  1 , Neha Jodhawat  1 , Aparna Dalvi  1 , Shweta Shinde  1 , Parag Tamhankar  2 , Priyanka Setia  1 , Priyanka Kambli  1 , Amruta Dhawale  1 , Lavina Temkar  1 , Disha Vedpathak  1 , Amrutha Jose  1 , Maya Gupta  1 , Reetika Yadav-Malik  1 , Shubhankar Dutta  3 , Kokoli Bose  3 , Prasad Taur  4 , Vijaya Gowri  4 , Vaishnavi Iyengar  4 , Akshaya Chougule  4 , Mukesh Desai  4 , Meena Sivasankaran  5 , Sagar Bhattad  6 , Sarath Balaji  7 , Sangeeta Mudaliar  8 , Ashruti Kacha  9 , Girish Subramanian  10 , Swati Patel  11 , Sujata Sharma  12 , Abhilasha Sampagar  13 , Manisha Madkaikar  14
Affiliations

Mutational Landscape of Patients with Wiskott Aldrich Syndrome: Update from India

Pallavi Gaikwad et al. J Clin Immunol. .

Abstract

Purpose: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: Clinical immunology; Cohort study; Inborn errors of immunity; Wiskott Aldrich Syndrome.

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Conflict of interest statement

Declarations. Ethical Approval: This study has been approved by Institutional Ethics committee (IEC)-National Institute of Immunohaematology (ICMR) Mumbai (Ref: NIIH/IEC/11-2016). Consent to Participate: We have received written informed consent from the patient's guardians. Consent for Publication: Informed consent has been signed by the guardians for publishing this data. Conflict of Interest: The authors declare that there are no conflicts of interest to disclose.

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