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Family-Based Next-Generation Sequencing Study Identifies an IL2RG Variant in an Infant with Primary Immunodeficiency.
OMICS 2019; 23(5):285-290O

Abstract

Primary immunodeficiencies (PIDs) are a rare and heterogeneous group of inherited genetic disorders that are characterized by an absent or impaired immune system. In this report, we describe the use of next-generation sequencing to investigate a male infant with clinical and immunological manifestations suggestive of a PID. Whole-exome sequencing of the infant along with his parents revealed a novel nucleotide variant (cytosine to adenine substitution at nucleotide position 252) in the coding region of the interleukin 2 receptor subunit gamma (IL2RG) gene. The mother was found to be a carrier. These findings are consistent with a diagnosis of X-linked severe combined immunodeficiency and represent the first such reported mutation in an Indian family. This mutation leads to an asparagine to lysine substitution (p.Asn84Lys) located in the extracellular domain of IL2RG, which is predicted to be pathogenic. Our study demonstrates the power of next-generation sequencing in identifying potential causative mutations to enable accurate clinical diagnosis, prenatal screening, and carrier female detection in PID patients. We believe that this approach, which is not a current routine in clinical practice, will become a mainstream component of individualized medicine in the near future.

Authors+Show Affiliations

1 Institute of Bioinformatics, Bangalore, India. 2 Manipal Academy of Higher Education, Manipal, Karnataka, India. 3 Center for Molecular Medicine, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India.4 Pediatric Hematology, Oncology and Bone Marrow Transplant, Mazumdar Shaw Medical Center, Narayana Health City, Bangalore, India.4 Pediatric Hematology, Oncology and Bone Marrow Transplant, Mazumdar Shaw Medical Center, Narayana Health City, Bangalore, India.1 Institute of Bioinformatics, Bangalore, India.1 Institute of Bioinformatics, Bangalore, India. 5 Amrita School of Biotechnology, Amrita Vishwa Vidyapeetham, Kollam, India.1 Institute of Bioinformatics, Bangalore, India.1 Institute of Bioinformatics, Bangalore, India. 2 Manipal Academy of Higher Education, Manipal, Karnataka, India. 3 Center for Molecular Medicine, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India. 6 Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota. 7 Center for Individualized Medicine, Mayo Clinic, Rochester, Minnesota.8 National Institute of Immunohaematology, KEM Hospital Campus, Mumbai, India.1 Institute of Bioinformatics, Bangalore, India.1 Institute of Bioinformatics, Bangalore, India. 2 Manipal Academy of Higher Education, Manipal, Karnataka, India. 3 Center for Molecular Medicine, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India.3 Center for Molecular Medicine, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India. 6 Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota. 7 Center for Individualized Medicine, Mayo Clinic, Rochester, Minnesota.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

31100039

Citation

Bandari, Aravind K., et al. "Family-Based Next-Generation Sequencing Study Identifies an IL2RG Variant in an Infant With Primary Immunodeficiency." Omics : a Journal of Integrative Biology, vol. 23, no. 5, 2019, pp. 285-290.
Bandari AK, Bhat S, Archana MV, et al. Family-Based Next-Generation Sequencing Study Identifies an IL2RG Variant in an Infant with Primary Immunodeficiency. OMICS. 2019;23(5):285-290.
Bandari, A. K., Bhat, S., Archana, M. V., Yadavalli, S., Patel, K., Rajagopalan, P., ... Pandey, A. (2019). Family-Based Next-Generation Sequencing Study Identifies an IL2RG Variant in an Infant with Primary Immunodeficiency. Omics : a Journal of Integrative Biology, 23(5), pp. 285-290. doi:10.1089/omi.2018.0196.
Bandari AK, et al. Family-Based Next-Generation Sequencing Study Identifies an IL2RG Variant in an Infant With Primary Immunodeficiency. OMICS. 2019;23(5):285-290. PubMed PMID: 31100039.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Family-Based Next-Generation Sequencing Study Identifies an IL2RG Variant in an Infant with Primary Immunodeficiency. AU - Bandari,Aravind K, AU - Bhat,Sunil, AU - Archana,M V, AU - Yadavalli,Sunita, AU - Patel,Krishna, AU - Rajagopalan,Pavithra, AU - Madugundu,Anil K, AU - Madkaikar,Manisha, AU - Reddy,Kavita, AU - Muthusamy,Babylakshmi, AU - Pandey,Akhilesh, PY - 2019/5/18/entrez PY - 2019/5/18/pubmed PY - 2019/5/18/medline KW - bone marrow transplantation KW - genetic defects KW - molecular diagnostics KW - newborn screening KW - next-generation sequencing KW - primary immunodeficiency SP - 285 EP - 290 JF - Omics : a journal of integrative biology JO - OMICS VL - 23 IS - 5 N2 - Primary immunodeficiencies (PIDs) are a rare and heterogeneous group of inherited genetic disorders that are characterized by an absent or impaired immune system. In this report, we describe the use of next-generation sequencing to investigate a male infant with clinical and immunological manifestations suggestive of a PID. Whole-exome sequencing of the infant along with his parents revealed a novel nucleotide variant (cytosine to adenine substitution at nucleotide position 252) in the coding region of the interleukin 2 receptor subunit gamma (IL2RG) gene. The mother was found to be a carrier. These findings are consistent with a diagnosis of X-linked severe combined immunodeficiency and represent the first such reported mutation in an Indian family. This mutation leads to an asparagine to lysine substitution (p.Asn84Lys) located in the extracellular domain of IL2RG, which is predicted to be pathogenic. Our study demonstrates the power of next-generation sequencing in identifying potential causative mutations to enable accurate clinical diagnosis, prenatal screening, and carrier female detection in PID patients. We believe that this approach, which is not a current routine in clinical practice, will become a mainstream component of individualized medicine in the near future. SN - 1557-8100 UR - https://www.unboundmedicine.com/medline/citation/31100039/Family-Based_Next-Generation_Sequencing_Study_Identifies_an_IL2RG_Variant_in_an_Infant_with_Primary_Immunodeficiency L2 - https://www.liebertpub.com/doi/full/10.1089/omi.2018.0196?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -