Spectrum of WAS gene mutations in Vietnamese patients with Wiskott–Aldrich syndrome

Pediatrics International - Tập 66 Số 1 - 2024
Ho Quoc Chuong1, Phan Thị Xinh2,3, Duong Bich Tram1,4, Nguyễn Thị Thanh Hà5, Tuan M. Nguyen6, Phan Nguyen Lien Anh6, Nguyen Dinh Van7, Nguyen Hoang Mai Anh8, Phu Chi Dung3, Nghia Dinh Huynh2,3, Hoàng Anh Vũ1
1Center for Molecular Biomedicine, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam
2Department of Hematology, Faculty of Medicine, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam.
3Ho Chi Minh City Blood Transfusion and Hematology Hospital, Ho Chi Minh City, Vietnam.
4Ho Chi Minh City Open University, Ho Chi Minh City, Vietnam
5Department of Molecular Biology, Dai Phuoc Clinic, Ho Chi Minh City, Vietnam.
6Department of Hematology Children's Hospital 1 Ho Chi Minh City Vietnam
7Department of Oncology and Hematology, Children's Hospital 2, Ho Chi Minh City, Vietnam
8Department of Hematology City Children's Hospital Ho Chi Minh City Vietnam

Tóm tắt

AbstractBackground

WAS gene mutational analysis is crucial to establish a definite diagnosis of Wiskott–Aldrich syndrome (WAS). Data on the genetic background of WAS in Vietnamese patients have not been reported.

Methods

We recruited 97 male, unrelated patients with WAS and analyzed WAS gene mutation using Sanger sequencing technology.

Results

We identified 36 distinct hemizygous pathogenic mutations, with 17 novel variants, from 38 patients in the entire cohort (39.2%). The mutational spectrum included 14 missense, 12 indel, five nonsense, four splicing, and one non‐stop mutations. Most mutations appear only once, with the exception of c.37C>T (p.R13X) and c.374G>A (p.G125E) each of which occurs twice in unrelated patients.

Conclusion

Our data enrich the mutational spectrum of the WAS gene and are crucial for understanding the genetic background of WAS and for supporting genetic counseling.

Từ khóa


Tài liệu tham khảo

10.2147/TACG.S213920

10.1182/blood-2003-05-1592

Eghbali M, 2016, Novel WASP mutation in a patient with Wiskott–Aldrich syndrome: case report and review of the literature, Allergol Immunopathol, 44, 450, 10.1016/j.aller.2015.11.002

Malik MA, 2024, Wiskott‐Aldrich Syndrome

10.3892/mmr.2017.7416

Thrasher AJ, 2000, The Wiskott–Aldrich syndrome, Clin Exp Allergy, 120, 2

10.1002/(SICI)1098-1004(200001)15:1<7::AID-HUMU4>3.0.CO;2-N

10.3389/fimmu.2021.627651

Kolluri R, 1995, Identification of WASP mutations in patients with Wiskott‐Aldrich syndrome and isolated thrombocytopenia reveals allelic heterogeneity at the WAS locus, Hum Mol Genet, 4, 1119, 10.1093/hmg/4.7.1119

10.1182/blood.V90.7.2680.2680_2680_2689

10.4049/jimmunol.175.2.1329

Lee WI, 2007, Clinical aspects and molecular analysis of Chinese patients with Wiskott‐Aldrich syndrome in Taiwan, Int Arch Allergy Immunol, 145, 15, 10.1159/000107462

10.1097/00130832-200312000-00003

10.1182/blood-2003-05-1480

10.2147/TACG.S58444

10.1016/j.jaci.2006.02.005

10.1016/j.jaci.2020.06.018

Massaad MJ, 2020, Encyclopedia of medical immunology: immunodeficiency diseases, 705, 10.1007/978-1-4614-8678-7_163

Kiet NC, 2019, Spectrum of mutations in the RB1 gene in Vietnamese patients with retinoblastoma, Mol Vis, 25, 215

Hamby SE, 2011, A meta‐analysis of single base‐pair substitutions in translational termination codons (‘nonstop’ mutations) that cause human inherited disease, Hum Genomics, 5, 1, 10.1186/1479-7364-5-4-241

10.1016/j.molimm.2010.11.013

10.1111/sji.12004

Ji X, 2022, Identification of a novel WAS mutation and the non‐splicing effect of a second‐site mutation in a Chinese pedigree with Wiskott–Aldrich syndrome, Orphanet J Rare Dis, 17, 447, 10.1186/s13023-022-02589-y