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Phenotypic Heterogeneity and Genotypic Spectrum of Primary Immunodeficiencies with Whole Exome Sequencing in a Thai Patient Cohort
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  • Maliwan Tengsujaritkul,
  • Narissara Suratannon,
  • Chupong Ittiwut,
  • Rungnapa Ittiwut,
  • Pantipa Chatchatee,
  • Kanya Suphapeetiporn,
  • Vorasuk Shotelersuk
Maliwan Tengsujaritkul
Chulalongkorn University Faculty of Medicine
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Narissara Suratannon
Chulalongkorn University Faculty of Medicine
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Chupong Ittiwut
Chulalongkorn University Faculty of Medicine
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Rungnapa Ittiwut
Chulalongkorn University Faculty of Medicine
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Pantipa Chatchatee
Chulalongkorn University
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Kanya Suphapeetiporn
Chulalongkorn University Faculty of Medicine
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Vorasuk Shotelersuk
Chulalongkorn University Faculty of Medicine
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Abstract

Background: Primary immunodeficiency diseases (PIDs) comprise more than 400 rare diseases with potential life-threatening conditions. Clinical manifestations and genetic defects are heterogeneous and diverse among populations. Here, we aimed to characterize the clinical, immunological and genetic features of Thai pediatric patients with PIDs. The use of whole exome sequencing (WES) in diagnosis and clinical decision making was also assessed. Methods: 36 unrelated patients with clinical and laboratory findings consistent with PIDs were recruited from January 2010 to December 2020. WES was performed to identify the underlying genetic defects. Results: The median age of disease onset was 4 months (range; 1 month to 13 years) and 24 were male (66.7%). Recurrent sinopulmonary tract infection was the most common clinical presentation followed by septicemia, and severe pneumonia. Using WES, we successfully identified the underlying genetic defects in 18 patients (50%). Of the 20 variants identified, six have not been previously described (30%). According to the International Union of Immunological Societies (IUIS), 38.9% of these detected cases (7/18) were found to harbor variants associated with genes in combined immunodeficiencies with associated or syndromic features (Class II). Conclusion: The diagnostic yield of WES in this patient cohort was 50%. Six novel genetic variants in PID genes were identified. The clinical usefulness of WES in PIDs was demonstrated, emphasizing it as an effective diagnostic strategy in these genetically heterogeneous disorders.

Peer review status:IN REVISION

28 Jul 2021Submitted to Pediatric Allergy and Immunology
06 Aug 2021Reviewer(s) Assigned
18 Aug 2021Review(s) Completed, Editorial Evaluation Pending
20 Aug 2021Editorial Decision: Revise Major