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LRBA deficiency in a patient with a novel homozygous mutation due to chromosome 4 segmental uniparental isodisomy

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dc.contributor.author Soler-Palacín, Pere
dc.contributor.author Garcia-Prat, Marina
dc.contributor.author Martín-Nalda, Andrea
dc.contributor.author Franco-Jarava, Clara
dc.contributor.author Rivière, Jacques G.
dc.contributor.author Plaja, Alberto
dc.contributor.author Bezdan, Daniela
dc.contributor.author Bosio, Mattia
dc.contributor.author Martínez-Gallo, Mónica
dc.contributor.author Ossowski, Stephan
dc.contributor.author Colobran, Roger
dc.date.accessioned 2019-11-15T08:12:58Z
dc.date.available 2019-11-15T08:12:58Z
dc.date.issued 2018
dc.identifier.citation Soler-Palacín P, Garcia-Prat M, Martín-Nalda A, Franco-Jarava C, Rivière JG, Plaja A et al. LRBA deficiency in a patient with a novel homozygous mutation due to chromosome 4 segmental uniparental isodisomy. Front Immunol. 2018;9:2397. DOI: 10.3389/fimmu.2018.02397
dc.identifier.issn 1664-3224
dc.identifier.uri http://hdl.handle.net/10230/42862
dc.description.abstract LRBA deficiency was first described in 2012 as an autosomal recessive disorder caused by biallelic mutations in the LRBA gene (OMIM #614700). It was initially characterized as producing early-onset hypogammaglobulinemia, autoimmune manifestations, susceptibility to inflammatory bowel disease, and recurrent infection. However, further reports expanded this phenotype (including patients without hypogammaglobulinemia) and described LRBA deficiency as a clinically variable syndrome with a wide spectrum of clinical manifestations. We present the case of a female patient who presented with type 1 diabetes, psoriasis, oral thrush, and enlarged liver and spleen at the age of 8 months. She later experienced recurrent bacterial and viral infections, including pneumococcal meningitis and Epstein Barr viremia. She underwent two consecutive stem cell transplants at the age of 8 and 9 years, and ultimately died. Samples from the patient and her parents were subjected to whole exome sequencing, which revealed a homozygous 1-bp insertion in exon 23 of the patient's LRBA gene, resulting in frameshift and premature stop codon. The patient's healthy mother was heterozygous for the mutation and her father tested wild-type. This finding suggested that either one copy of the paternal chromosome 4 bore a deletion including the LRBA locus, or the patient inherited two copies of the mutant maternal LRBA allele. The patient's sequencing data showed a 1-Mb loss of heterozygosity region in chromosome 4, including the LRBA gene. Comparative genomic hybridization array of the patient's and father's genomic DNA yielded normal findings, ruling out genomic copy number abnormalities. Here, we present the first case of LRBA deficiency due to a uniparental disomy (UPD). In contrast to classical Mendelian inheritance, UPD involves inheritance of 2 copies of a chromosomal region from only 1 parent. Specifically, our patient carried a small segmental isodisomy of maternal origin affecting 1 Mb of chromosome 4.
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher Frontiers
dc.relation.ispartof Frontiers in Immunology. 2018;9:2397
dc.rights © 2018 Soler-Palacín, Garcia-Prat, Martín-Nalda, Franco-Jarava, Rivière, Plaja, Bezdan, Bosio, Martínez-Gallo, Ossowski and Colobran. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) (http://creativecommons.org/licenses/by/4.0/). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
dc.rights.uri http://creativecommons.org/licenses/by/4.0/
dc.title LRBA deficiency in a patient with a novel homozygous mutation due to chromosome 4 segmental uniparental isodisomy
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.3389/fimmu.2018.02397
dc.subject.keyword Primary immunodeficiency
dc.subject.keyword LRBA deficiency
dc.subject.keyword Uniparental disomy
dc.subject.keyword Whole exome sequencing
dc.subject.keyword Comparative genomic hybridization array
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion


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