Novel compound heterozygous stop-gain mutations of LRBA in a Vietnamese patient with Common Variable Immune Deficiency.

Molecular Genetics & Genomic Medicine
Anh N L PhanChi-Bao Bui

Abstract

Lipopolysaccharide-responsive and beige-like anchor (LRBA) deficiency is a rare autosomal recessive common variable immunodeficiency (CVID), affecting 1:25,000-1:50,000 people worldwide. Biallelic mutations in the gene LRBA have been implicated in affected individuals. We report a 16-year-old Vietnamese, male patient with recurrent CVID symptoms including chronic diarrhea, interstitial pneumonia, cutaneous granulomatous lesions, hepatosplenomegaly, and finger clubbing. Immunological analyses and whole exome sequencing (WES) were performed to investigate phenotypic and genotypic features. Immunological analyses revealed hypogammaglobulinemia and low ratios of CD4+/CD8+ T cells. Two novel compound heterozygous stop-gain mutation in LRBA were identified: c.1933C > T (p.R645X) and c.949C > T (p.R317X). Sanger sequencing confirmed the segregation of these variants from the intact parents. The abolished LRBA protein expression was shown by immunoblot analysis. Subsequent treatment potentially saves the child from the same immune thrombocytopenia which led to his brother's untimely death; likely caused by the same LRBA mutations. This first report of LRBA deficiency in Vietnam expands our knowledge of the diverse phenotypes and genoty...Continue Reading

References

Mar 20, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·J W WangW G Kerr
May 23, 2012·American Journal of Human Genetics·Gabriela Lopez-HerreraBodo Grimbacher
Mar 4, 2014·The Journal of Allergy and Clinical Immunology·Benjamin GathmannUNKNOWN European Society for Immunodeficiencies Registry Working Party
Mar 6, 2015·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Sue RichardsUNKNOWN ACMG Laboratory Quality Assurance Committee
Dec 29, 2015·Journal of Clinical Immunology·Omar K AlkhairyLennart Hammarström
Jan 16, 2016·The Journal of Allergy and Clinical Immunology·Laura Gámez-DíazBodo Grimbacher
Jul 6, 2016·Frontiers in Immunology·Patrick MaffucciCharlotte Cunningham-Rundles
Jan 31, 2017·American Journal of Human Genetics·Quan Li, Kai Wang
May 16, 2017·The Journal of Allergy and Clinical Immunology·Markus G SeidelUNKNOWN Inborn Errors Working Party of the European Group for Blood and Marrow Transplantation
Jun 12, 2017·The Journal of Allergy and Clinical Immunology·Fayhan J AlroqiTalal A Chatila
Sep 29, 2017·Journal of Clinical Immunology·Sevgi Kostel BalAydan Ikinciogullari
Nov 28, 2018·JMM Case Reports·Sanem Eren AkarcanNecil Kutukculer
Jun 11, 2019·Human Mutation·Vinh S LeLiem T Nguyen
Dec 31, 2019·The Journal of Allergy and Clinical Immunology·Victoria Katharina TeschUNKNOWN Inborn Errors, Clinical, and Registry Working Parties of the European Society for Blood and Marrow Transplantation and the E

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Citations

Jun 12, 2021·Molecular Genetics & Genomic Medicine·Anh Nguyen Lien PhanPetrus Martinus Van Hagen
Jun 22, 2021·Current Opinion in Immunology·Neftali J RamirezBodo Grimbacher

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Methods Mentioned

BETA
flow cytometry
biopsy
exome sequencing

Software Mentioned

MutationTaster
LRT
AMP
GERP
DANN

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