The dilemma of X-linked agammaglobulinemia carriers
Background: Many patients with X-linked agammaglobulinemia (XLA) nowadays have reached adulthood, as well as their sisters, possibly carriers of a deleterious Bruton tyrosine kinase variant. Studies on motherhood outcomes in families with XLA are lacking. Objective: We sought to investigate adherenc...
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2025-02-01
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| Series: | Journal of Allergy and Clinical Immunology: Global |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2772829324001802 |
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| author | Federica Pulvirenti, MD, PhD Cinzia Milito, MD, PhD Francesco Cinetto, MD, PhD Giulia Garzi, MD Germano Sardella, MD Giuseppe Spadaro, MD Francesca Lippi, MD Valentina Guarnieri, MD Bianca Laura Cinicola, MD Maria Carrabba, MD, PhD Daniele Guadagnolo, MD Giovanna Fabio, MD Baldassarre Martire, MD Caterina Cancrini, MD, PhD Giulia Lanzoni, MD Andrea Finocchi, MD, PhD Gigliola Di Matteo, MD, PhD Eva Pompilii, MD Simona Ferrari, BD, PhD Isabella Quinti, MD, PhD |
| author_facet | Federica Pulvirenti, MD, PhD Cinzia Milito, MD, PhD Francesco Cinetto, MD, PhD Giulia Garzi, MD Germano Sardella, MD Giuseppe Spadaro, MD Francesca Lippi, MD Valentina Guarnieri, MD Bianca Laura Cinicola, MD Maria Carrabba, MD, PhD Daniele Guadagnolo, MD Giovanna Fabio, MD Baldassarre Martire, MD Caterina Cancrini, MD, PhD Giulia Lanzoni, MD Andrea Finocchi, MD, PhD Gigliola Di Matteo, MD, PhD Eva Pompilii, MD Simona Ferrari, BD, PhD Isabella Quinti, MD, PhD |
| author_sort | Federica Pulvirenti, MD, PhD |
| collection | DOAJ |
| description | Background: Many patients with X-linked agammaglobulinemia (XLA) nowadays have reached adulthood, as well as their sisters, possibly carriers of a deleterious Bruton tyrosine kinase variant. Studies on motherhood outcomes in families with XLA are lacking. Objective: We sought to investigate adherence to carrier status screening, interest in preconception and prenatal genetic counseling, and reproductive decisions in relatives with XLA. Methods: In this multicenter, retrospective cohort study, we collected a 3-generation pedigree and data on mothers and sisters of patients with XLA, including carrier status and pregnancy outcome. Results: Data on 53 adults with XLA, 52 mothers, and 33 sisters were collected. All XLA sisters received genetic counseling. Forty percent of the sisters chose to undergo carrier status determination, and 60% of them chose invasive prenatal testing. The main reasons for the sisters to decide not to undergo genetic testing were their young age and the willingness to carry on with the pregnancy regardless of the outcome of the genetic test, followed by the willingness to postpone the decision at the time of pregnancy and the decision to not have children. Prenatal testing resulted in 5 XLA diagnoses, with 2 pregnancy terminations, 1 miscarriage, and 2 XLA live births. Three carriers refused prenatal testing and had 6 live births, including 3 XLA-affected sons. One sister was diagnosed as a carrier after the birth of an XLA-affected son. In total, 9 XLA diagnoses were made, including 6 live births. Conclusions: A number of XLA sister carriers decided to carry on with their pregnancy after receiving the diagnosis of an affected fetus or after refusing prenatal testing. We propose to initiate a more extensive collaborative study to verify the effect of genetic counseling on families with XLA in other cohorts from different countries. |
| format | Article |
| id | doaj-art-c574108a7e0744129472bfc4287a05a6 |
| institution | Kabale University |
| issn | 2772-8293 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
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| series | Journal of Allergy and Clinical Immunology: Global |
| spelling | doaj-art-c574108a7e0744129472bfc4287a05a62025-01-08T04:53:51ZengElsevierJournal of Allergy and Clinical Immunology: Global2772-82932025-02-0141100384The dilemma of X-linked agammaglobulinemia carriersFederica Pulvirenti, MD, PhD0Cinzia Milito, MD, PhD1Francesco Cinetto, MD, PhD2Giulia Garzi, MD3Germano Sardella, MD4Giuseppe Spadaro, MD5Francesca Lippi, MD6Valentina Guarnieri, MD7Bianca Laura Cinicola, MD8Maria Carrabba, MD, PhD9Daniele Guadagnolo, MD10Giovanna Fabio, MD11Baldassarre Martire, MD12Caterina Cancrini, MD, PhD13Giulia Lanzoni, MD14Andrea Finocchi, MD, PhD15Gigliola Di Matteo, MD, PhD16Eva Pompilii, MD17Simona Ferrari, BD, PhD18Isabella Quinti, MD, PhD19Reference Centre for Primary Immune Deficiencies, Sapienza University Hospital Policlinico Umberto I, Rome, ItalyDepartment of Molecular Medicine, Sapienza University, Rome, ItalyRare Diseases Referral Center, Internal Medicine 1, Ca’ Foncello Hospital, Treviso, Department of Medicine—DIMED, University of Padova, Padua, ItalyDepartment of Molecular Medicine, Sapienza University, Rome, ItalyDepartment of Translational and Precision Medicine, Sapienza University of Rome, Rome, ItalyDepartment of Translational Medical Sciences, University of Naples Federico II, Naples, ItalyImmunology Division, Section of Pediatrics, Meyer Children’s Hospital IRCCS, Florence, ItalyImmunology Division, Section of Pediatrics, Meyer Children’s Hospital IRCCS, Florence, ItalyDepartment of Molecular Medicine, Sapienza University, Rome, Italy; Department of Maternal Infantile and Urological Sciences, Sapienza University of Rome, Rome, ItalyDepartment of Medicine, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, ItalyDepartment of Molecular Medicine, Sapienza University, Rome, ItalyDepartment of Medicine, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, ItalyPediatrics and Neonatology Unit, Maternal-Infant Department, Monsignor A. R. Dimiccoli Hospital, Barletta, ItalyResearch Unit of Primary Immunodeficiencies, Academic Department of Pediatrics, UOC Clinical Immunology and Vaccinology IRCCS Bambino Gesù Children’s Hospital, Rome, Italy; Department of Systems Medicine University of Rome Tor Vergata, Rome, ItalyMedical Genetics Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, ItalyResearch Unit of Primary Immunodeficiencies, Academic Department of Pediatrics, UOC Clinical Immunology and Vaccinology IRCCS Bambino Gesù Children’s Hospital, Rome, Italy; Department of Systems Medicine University of Rome Tor Vergata, Rome, ItalyResearch Unit of Primary Immunodeficiencies, Academic Department of Pediatrics, UOC Clinical Immunology and Vaccinology IRCCS Bambino Gesù Children’s Hospital, Rome, Italy; Department of Systems Medicine University of Rome Tor Vergata, Rome, ItalyNext Fertility GynePro, NextClinics International, Bologna, ItalyNext Fertility GynePro, NextClinics International, Bologna, ItalyDepartment of Molecular Medicine, Sapienza University, Rome, Italy; Corresponding author: Isabella Quinti, MD, PhD, Department of Molecular Medicine, Sapienza University, Viale Regina Elena 291, Rome 00161, Italy.Background: Many patients with X-linked agammaglobulinemia (XLA) nowadays have reached adulthood, as well as their sisters, possibly carriers of a deleterious Bruton tyrosine kinase variant. Studies on motherhood outcomes in families with XLA are lacking. Objective: We sought to investigate adherence to carrier status screening, interest in preconception and prenatal genetic counseling, and reproductive decisions in relatives with XLA. Methods: In this multicenter, retrospective cohort study, we collected a 3-generation pedigree and data on mothers and sisters of patients with XLA, including carrier status and pregnancy outcome. Results: Data on 53 adults with XLA, 52 mothers, and 33 sisters were collected. All XLA sisters received genetic counseling. Forty percent of the sisters chose to undergo carrier status determination, and 60% of them chose invasive prenatal testing. The main reasons for the sisters to decide not to undergo genetic testing were their young age and the willingness to carry on with the pregnancy regardless of the outcome of the genetic test, followed by the willingness to postpone the decision at the time of pregnancy and the decision to not have children. Prenatal testing resulted in 5 XLA diagnoses, with 2 pregnancy terminations, 1 miscarriage, and 2 XLA live births. Three carriers refused prenatal testing and had 6 live births, including 3 XLA-affected sons. One sister was diagnosed as a carrier after the birth of an XLA-affected son. In total, 9 XLA diagnoses were made, including 6 live births. Conclusions: A number of XLA sister carriers decided to carry on with their pregnancy after receiving the diagnosis of an affected fetus or after refusing prenatal testing. We propose to initiate a more extensive collaborative study to verify the effect of genetic counseling on families with XLA in other cohorts from different countries.http://www.sciencedirect.com/science/article/pii/S2772829324001802XLABrutoncarriergenetic counselingprenatal testingpregnancies |
| spellingShingle | Federica Pulvirenti, MD, PhD Cinzia Milito, MD, PhD Francesco Cinetto, MD, PhD Giulia Garzi, MD Germano Sardella, MD Giuseppe Spadaro, MD Francesca Lippi, MD Valentina Guarnieri, MD Bianca Laura Cinicola, MD Maria Carrabba, MD, PhD Daniele Guadagnolo, MD Giovanna Fabio, MD Baldassarre Martire, MD Caterina Cancrini, MD, PhD Giulia Lanzoni, MD Andrea Finocchi, MD, PhD Gigliola Di Matteo, MD, PhD Eva Pompilii, MD Simona Ferrari, BD, PhD Isabella Quinti, MD, PhD The dilemma of X-linked agammaglobulinemia carriers Journal of Allergy and Clinical Immunology: Global XLA Bruton carrier genetic counseling prenatal testing pregnancies |
| title | The dilemma of X-linked agammaglobulinemia carriers |
| title_full | The dilemma of X-linked agammaglobulinemia carriers |
| title_fullStr | The dilemma of X-linked agammaglobulinemia carriers |
| title_full_unstemmed | The dilemma of X-linked agammaglobulinemia carriers |
| title_short | The dilemma of X-linked agammaglobulinemia carriers |
| title_sort | dilemma of x linked agammaglobulinemia carriers |
| topic | XLA Bruton carrier genetic counseling prenatal testing pregnancies |
| url | http://www.sciencedirect.com/science/article/pii/S2772829324001802 |
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