. 2024 Jul 2;44(7):157.

doi: 10.1007/s10875-024-01759-w.

Genetic Evaluation of the Patients with Clinically Diagnosed Inborn Errors of Immunity by Whole Exome Sequencing: Results from a Specialized Research Center for Immunodeficiency in Türkiye

Baran Erman^{1

2}, Umran Aba^{3

4}, Canberk Ipsir^{3

4}, Damla Pehlivan³, Caner Aytekin⁵, Gökhan Cildir⁶, Begum Cicek⁷, Ceren Bozkurt³, Sidem Tekeoglu³, Melisa Kaya³, Cigdem Aydogmus⁸, Funda Cipe⁹, Gulsan Sucak¹⁰, Sevgi Bilgic Eltan¹¹, Ahmet Ozen¹¹, Safa Barıs¹¹, Elif Karakoc-Aydiner¹¹, Ayca Kıykım¹², Betul Karaatmaca¹³, Hulya Kose¹⁴, Dilara Fatma Kocacık Uygun¹⁵, Fatih Celmeli¹⁶, Tugba Arikoglu¹⁷, Dilek Ozcan¹⁸, Ozlem Keskin¹⁹, Elif Arık¹⁹, Elif Soyak Aytekin²⁰, Mahmut Cesur¹⁹, Ercan Kucukosmanoglu¹⁹, Mehmet Kılıc²¹, Mutlu Yuksek²², Zafer Bıcakcı²³, Saliha Esenboga²⁴, Deniz Çagdaş Ayvaz^{24

25}, Asena Pınar Sefer²⁶, Sukrü Nail Guner²⁷, Sevgi Keles²⁷, Ismail Reisli²⁷, Ugur Musabak²⁸, Nazlı Deveci Demirbas²⁹, Sule Haskologlu²⁹, Sara Sebnem Kilic^{30

31}, Ayse Metin¹³, Figen Dogu²⁹, Aydan Ikinciogulları^#²⁹, Ilhan Tezcan^#²⁴

Affiliations

¹ Institute of Child Health, Hacettepe University, Ankara, Turkey. baranerman@gmail.com.
² Can Sucak Research Laboratory for Translational Immunology, Hacettepe University, Ankara, Turkey. baranerman@gmail.com.
³ Can Sucak Research Laboratory for Translational Immunology, Hacettepe University, Ankara, Turkey.
⁴ Department of Pediatric Immunology, Institute of Child Health, Hacettepe University, Ankara, Turkey.
⁵ Pediatric Immunology, SBU Ankara Dr Sami Ulus Maternity Child Health and Diseases Training and Research Hospital, Ankara, Turkey.
⁶ Centre for Cancer Biology, University of South Australia and SA Pathology, Adelaide, SA, 5000, Australia.
⁷ Institute of Child Health, Hacettepe University, Ankara, Turkey.
⁸ Department of Pediatric Allergy and Clinical Immunology, University of Health Sciences, Istanbul Basaksehir Cam and Sakura City Hospital, Istanbul, Turkey.
⁹ Department of Pediatric Allergy and Clinical Immunology, Altinbas University School of Medicine, Istanbul, Turkey.
¹⁰ Medical Park Bahçeşehir Hospital, Clinic of Hematology and Transplantation, İstanbul, Turkey.
¹¹ Marmara University, Faculty of Medicine, Department of Pediatric Allergy and Immunology, Jeffrey Modell Diagnostic and Research Center for Primary Immunodeficiencies, The Isil Berat Barlan Center for Translational Medicine, Istanbul, Turkey.
¹² Pediatric Allergy and Immunology, Cerrahpasa School of Medicine, Istanbul University-Cerrahpasa, Istanbul, Turkey.
¹³ Department of Pediatric Allergy and Immunology, University of Health Sciences, Ankara Bilkent City Hospital, Ankara, Turkey.
¹⁴ Department of Pediatric Immunology, Diyarbakir Children Hospital, Diyarbakır, Turkey.
¹⁵ Division of Allergy Immunology, Department of Pediatrics, Akdeniz University Faculty of Medicine, Antalya, Turkey.
¹⁶ Republic of Turkey Ministry of Health Antalya Training and Research Hospital Pediatric Immunology and Allergy Diseases, Antalya, Turkey.
¹⁷ Department of Pediatric Allergy and Immunology, Faculty of Medicine, Mersin University, Mersin, Turkey.
¹⁸ Division of Pediatric Allergy and Immunology, Faculty of Medicine, Balcali Hospital, Cukurova University, Adana, Turkey.
¹⁹ Department of Pediatric Allergy and Immunology, Faculty of Medicine, Gaziantep University, Gaziantep, Turkey.
²⁰ Department of Pediatric Allergy and Immunology, Etlik City Hospital, Ankara, Turkey.
²¹ Division of Allergy and Immunology, Department of Pediatrics, Faculty of Medicine, University of Firat, Elazığ, Turkey.
²² Department of Pediatric Immunology and Allergy, Faculty of Medicine, Zonguldak Bulent Ecevit University, Zonguldak, Turkey.
²³ Department of Pediatric Hematology, Faculty of Medicine, Ataturk University, Erzurum, Turkey.
²⁴ Department of Pediatrics, Division of Pediatric Immunology, Hacettepe University School of Medicine, Ankara, Turkey.
²⁵ Section of Pediatric Immunology, Institute of Child Health, Hacettepe University, Ankara, Turkey.
²⁶ Department of Pediatric Allergy and Immunology, Şanlıurfa Training and Research Hospital, Şanlıurfa, Turkey.
²⁷ Department of Pediatric Immunology and Allergy, Medicine Faculty, Necmettin Erbakan University, Konya, Turkey.
²⁸ Department of Immunology and Allergy, Baskent University School of Medicine, Ankara, Turkey.
²⁹ Department of Pediatric Immunology and Allergy, Ankara University Faculty of Medicine, Ankara, Turkey.
³⁰ Division of Pediatric Immunology-Rheumatology, Bursa Uludag University Faculty of Medicine, Bursa, Turkey.
³¹ Translational Medicine, Bursa Uludag University, Bursa, Turkey.

^# Contributed equally.

PMID: 38954121
PMCID: PMC11219406
DOI: 10.1007/s10875-024-01759-w

Genetic Evaluation of the Patients with Clinically Diagnosed Inborn Errors of Immunity by Whole Exome Sequencing: Results from a Specialized Research Center for Immunodeficiency in Türkiye

Baran Erman et al. J Clin Immunol. 2024.

. 2024 Jul 2;44(7):157.

doi: 10.1007/s10875-024-01759-w.

Authors

Affiliations

¹ Institute of Child Health, Hacettepe University, Ankara, Turkey. baranerman@gmail.com.
² Can Sucak Research Laboratory for Translational Immunology, Hacettepe University, Ankara, Turkey. baranerman@gmail.com.
³ Can Sucak Research Laboratory for Translational Immunology, Hacettepe University, Ankara, Turkey.
⁴ Department of Pediatric Immunology, Institute of Child Health, Hacettepe University, Ankara, Turkey.
⁵ Pediatric Immunology, SBU Ankara Dr Sami Ulus Maternity Child Health and Diseases Training and Research Hospital, Ankara, Turkey.
⁶ Centre for Cancer Biology, University of South Australia and SA Pathology, Adelaide, SA, 5000, Australia.
⁷ Institute of Child Health, Hacettepe University, Ankara, Turkey.
⁸ Department of Pediatric Allergy and Clinical Immunology, University of Health Sciences, Istanbul Basaksehir Cam and Sakura City Hospital, Istanbul, Turkey.
⁹ Department of Pediatric Allergy and Clinical Immunology, Altinbas University School of Medicine, Istanbul, Turkey.
¹⁰ Medical Park Bahçeşehir Hospital, Clinic of Hematology and Transplantation, İstanbul, Turkey.
¹¹ Marmara University, Faculty of Medicine, Department of Pediatric Allergy and Immunology, Jeffrey Modell Diagnostic and Research Center for Primary Immunodeficiencies, The Isil Berat Barlan Center for Translational Medicine, Istanbul, Turkey.
¹² Pediatric Allergy and Immunology, Cerrahpasa School of Medicine, Istanbul University-Cerrahpasa, Istanbul, Turkey.
¹³ Department of Pediatric Allergy and Immunology, University of Health Sciences, Ankara Bilkent City Hospital, Ankara, Turkey.
¹⁴ Department of Pediatric Immunology, Diyarbakir Children Hospital, Diyarbakır, Turkey.
¹⁵ Division of Allergy Immunology, Department of Pediatrics, Akdeniz University Faculty of Medicine, Antalya, Turkey.
¹⁶ Republic of Turkey Ministry of Health Antalya Training and Research Hospital Pediatric Immunology and Allergy Diseases, Antalya, Turkey.
¹⁷ Department of Pediatric Allergy and Immunology, Faculty of Medicine, Mersin University, Mersin, Turkey.
¹⁸ Division of Pediatric Allergy and Immunology, Faculty of Medicine, Balcali Hospital, Cukurova University, Adana, Turkey.
¹⁹ Department of Pediatric Allergy and Immunology, Faculty of Medicine, Gaziantep University, Gaziantep, Turkey.
²⁰ Department of Pediatric Allergy and Immunology, Etlik City Hospital, Ankara, Turkey.
²¹ Division of Allergy and Immunology, Department of Pediatrics, Faculty of Medicine, University of Firat, Elazığ, Turkey.
²² Department of Pediatric Immunology and Allergy, Faculty of Medicine, Zonguldak Bulent Ecevit University, Zonguldak, Turkey.
²³ Department of Pediatric Hematology, Faculty of Medicine, Ataturk University, Erzurum, Turkey.
²⁴ Department of Pediatrics, Division of Pediatric Immunology, Hacettepe University School of Medicine, Ankara, Turkey.
²⁵ Section of Pediatric Immunology, Institute of Child Health, Hacettepe University, Ankara, Turkey.
²⁶ Department of Pediatric Allergy and Immunology, Şanlıurfa Training and Research Hospital, Şanlıurfa, Turkey.
²⁷ Department of Pediatric Immunology and Allergy, Medicine Faculty, Necmettin Erbakan University, Konya, Turkey.
²⁸ Department of Immunology and Allergy, Baskent University School of Medicine, Ankara, Turkey.
²⁹ Department of Pediatric Immunology and Allergy, Ankara University Faculty of Medicine, Ankara, Turkey.
³⁰ Division of Pediatric Immunology-Rheumatology, Bursa Uludag University Faculty of Medicine, Bursa, Turkey.
³¹ Translational Medicine, Bursa Uludag University, Bursa, Turkey.

^# Contributed equally.

PMID: 38954121
PMCID: PMC11219406
DOI: 10.1007/s10875-024-01759-w

Erratum in

Correction to: Genetic Evaluation of the Patients with Clinically Diagnosed Inborn Errors of Immunity by Whole Exome Sequencing: Results from a Specialized Research Center for Immunodeficiency in Türkiye.
Erman B, Aba U, Ipsir C, Pehlivan D, Aytekin C, Cildir G, Cicek B, Bozkurt C, Tekeoglu S, Kaya M, Aydogmus C, Cipe F, Sucak G, Eltan SB, Ozen A, Barıs S, Karakoc-Aydiner E, Kıykım A, Karaatmaca B, Kose H, Uygun DFK, Celmeli F, Arikoglu T, Ozcan D, Keskin O, Arık E, Aytekin ES, Cesur M, Kucukosmanoglu E, Kılıc M, Yuksek M, Bıcakcı Z, Esenboga S, Ayvaz DÇ, Sefer AP, Guner SN, Keles S, Reisli I, Musabak U, Demirbas ND, Haskologlu S, Kilic SS, Metin A, Dogu F, Ikinciogulları A, Tezcan I. Erman B, et al. J Clin Immunol. 2024 Nov 14;45(1):41. doi: 10.1007/s10875-024-01841-3. J Clin Immunol. 2024. PMID: 39540960 Free PMC article. No abstract available.

Abstract

Molecular diagnosis of inborn errors of immunity (IEI) plays a critical role in determining patients' long-term prognosis, treatment options, and genetic counseling. Over the past decade, the broader utilization of next-generation sequencing (NGS) techniques in both research and clinical settings has facilitated the evaluation of a significant proportion of patients for gene variants associated with IEI. In addition to its role in diagnosing known gene defects, the application of high-throughput techniques such as targeted, exome, and genome sequencing has led to the identification of novel disease-causing genes. However, the results obtained from these different methods can vary depending on disease phenotypes or patient characteristics. In this study, we conducted whole-exome sequencing (WES) in a sizable cohort of IEI patients, consisting of 303 individuals from 21 different clinical immunology centers in Türkiye. Our analysis resulted in likely genetic diagnoses for 41.1% of the patients (122 out of 297), revealing 52 novel variants and uncovering potential new IEI genes in six patients. The significance of understanding outcomes across various IEI cohorts cannot be overstated, and we believe that our findings will make a valuable contribution to the existing literature and foster collaborative research between clinicians and basic science researchers.

Keywords: Inborn errors of immunity; genetic diagnosis; next generation sequencing; whole exome sequencing.

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing interests.

Figures

**Fig. 1**
Schematic workflow of the study

**Fig. 2**
Patient and variant characteristics. A Distribution of the patients based on their clinical diagnosis. B Diagnostic yield of the patients. C Number of the detected variants and their distribution across different IEI genes. D Types of detected variants and their novelty. E Distribution of zygosity. F Number of diagnosis in patient groups

See this image and copyright information in PMC

References

1. Notarangelo LD, Bacchetta R, Casanova JL, Su HC. Human inborn errors of immunity: An expanding universe. Sci Immunol. 2020;5(49) - PMC - PubMed
1. Eldeniz FC, Gul Y, Yorulmaz A, Guner SN, Keles S, Reisli I. Evaluation of the 10 Warning Signs in Primary and Secondary Immunodeficient Patients. Front Immunol. 2022;13:900055. - PMC - PubMed
1. Meyts I, Bousfiha A, Duff C, Singh S, Lau YL, Condino-Neto A, et al. Primary Immunodeficiencies: A Decade of Progress and a Promising Future. Front Immunol. 2020;11:625753. - PMC - PubMed
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1. Conley ME, Casanova JL. Discovery of single-gene inborn errors of immunity by next generation sequencing. Curr Opin Immunol. 2014;30:17–23. - PMC - PubMed

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Genetic Evaluation of the Patients with Clinically Diagnosed Inborn Errors of Immunity by Whole Exome Sequencing: Results from a Specialized Research Center for Immunodeficiency in Türkiye

Affiliations

Genetic Evaluation of the Patients with Clinically Diagnosed Inborn Errors of Immunity by Whole Exome Sequencing: Results from a Specialized Research Center for Immunodeficiency in Türkiye

Authors

Affiliations

Erratum in

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

LinkOut - more resources

Full Text Sources

Miscellaneous