Web of Science: 1 cites, Scopus: 1 cites, Google Scholar: cites,
Common Variable Immunodeficiency and Neurodevelopmental Delay Due to a 13Mb Deletion on Chromosome 4 Including the NFKB1 Gene : A Case Report
Franco-Jarava, Clara (Hospital Universitari Vall d'Hebron)
Valenzuela, Irene (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Riviere, Jacques G. (Hospital Universitari Vall d'Hebron)
Garcia-Prat, Marina (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Martínez Gallo, Mónica (Jeffrey Modell Diagnostic and Research Center for Primary Immunodeficiencies)
Dieli-Crimi, Romina (Jeffrey Modell Diagnostic and Research Center for Primary Immunodeficiencies)
Castells Sarret, Neus (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Batlle-Masó, Laura (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Soler-Palacín, Pere (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Colobrán Oriol, Roger (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Universitat Autònoma de Barcelona

Data: 2022
Resum: Syndromic immunodeficiencies are a heterogeneous group of inborn errors of immunity that can affect the development of non-immune organs and systems. The genetic basis of these immunodeficiencies is highly diverse, ranging from monogenic defects to large chromosomal aberrations. Antibody deficiency is the most prevalent immunological abnormality in patients with syndromic immunodeficiencies caused by chromosomal rearrangements, and usually manifests as a common variable immunodeficiency (CVID)-like phenotype. Here we describe a patient with a complex phenotype, including neurodevelopmental delay, dysmorphic features, malformations, and CVID (hypogammaglobulinemia, reduced pre-switch and switch memory B cells, and impaired vaccine response). Microarray-based comparative genomic hybridization (aCGH) revealed a 13-Mb deletion on chromosome 4q22. 2-q24 involving 53 genes, some of which were related to the developmental manifestations in our patient. Although initially none of the affected genes could be linked to his CVID phenotype, subsequent reanalysis identified NFKB1 haploinsufficiency as the cause. This study underscores the value of periodic reanalysis of unsolved genetic studies performed with high-throughput technologies (eg, next-generation sequencing and aCGH). This is important because of the ongoing incorporation of new data establishing the relationship between genes and diseases. In the present case, NFKB1 had not been associated with human disease at the time aCGH was performed. Eight years later, reanalysis of the genes included in the chromosome 4 deletion enabled us to identify NFKB1 haploinsufficiency as the genetic cause of our patient's CVID. In the future, other genes included in the deletion may be linked to human disease, allowing us to better define the molecular basis of our patient's complex clinical phenotype.
Ajuts: Instituto de Salud Carlos III PI17/00660
Instituto de Salud Carlos III PI20/00761
Drets: Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. Creative Commons
Llengua: Anglès
Document: Article ; recerca ; Versió publicada
Matèria: Primary immunodeficiencies ; Syndromic immunodeficiencies ; Common variable immunodeficiency ; Nfkb1 ; Chromosomal rearrangements
Publicat a: Frontiers in immunology, Vol. 13 (june 2022) , ISSN 1664-3224

DOI: 10.3389/fimmu.2022.897975
PMID: 35784294


8 p, 1.6 MB

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