Immune deficiencies, infection, and systemic immune disordersPrimary T-cell immunodeficiency with immunodysregulation caused by autosomal recessive LCK deficiency
Section snippets
Methods
Details of the materials and methods used in this study are provided in the Methods section in this article's Online Repository at www.jacionline.org. We obtained written informed consent for participation in the study from the parents of the patient. This study was approved by the institutional review board at Necker-Enfants Malades Hospital, and all experiments were carried out in accordance with the Helsinki Declaration.
Clinical features
We examined a child conceived by means of in vitro fertilization and born at term to healthy nonconsanguineous parents from France. Her birth weight was normal, and she was vaccinated at birth with BCG with no adverse effect. She had received 4 heptavalent conjugate vaccines against pneumococcus and 4 pentavalent vaccinations against Haemophilus influenzae type b, diphtheria, Bordetella pertussis, tetanus, and poliovirus at the ages of 2, 4, 6, and 14 months. She also received 2 immunizations
Discussion
We report here the first case of human LCK deficiency caused by complete maternal UPD of chromosome 1, which harbored the mutated LCK gene. UPD accounts for this recessive form of pediatric primary immunodeficiency in this patient, with the LCK germinal mutation being absent in the father and present in the patient's mother in the heterozygous state. UPD is defined as the inheritance of a pair of duplicated chromosomes from a single parent, and it is associated with 2 principal types of
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Supported by grants from INSERM, Agence Nationale de la Recherche (ANR-08-MIEN-012-01, France), and the European Research Council (ERC-2009-AdG_20090506 no. FP7-249816). S.L. is a senior scientist at the Centre National de la Recherche Scientifique (France) and F.H. is a clinician at the University Children's Hospital of Dresden (Germany) and holds fellowships from the German Research Council/DFG (HA 5967/1-1) and the Fondation IMAGINE (France). S.G. holds a fellowship from the Ministère de la Recherche and l'Ecole Polytechnique (France) and the Fondation ARC pour la Recherche sur le Cancer (ARC) (France). E.M. is supported by the ANR (France). D.M. received a Robert A. Good/Jeffrey Modell fellowship.
Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest.
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These authors contributed equally to this work.