Chronic granulomatous disease caused by maternal uniparental isodisomy of chromosome 16

García-Morato, María Bravo; Nevado, Julián; González‐Granado, Luis Ignacio; Urgelles, Ana Sastre; Pena, Rebeca Rodríguez; Cerdán, Antonio Ferreira

doi:10.1016/j.jaip.2017.01.018

Cited by 9 publications

(3 citation statements)

References 8 publications

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“…One case resulted from a uniparental isodisomy. Uniparental isodisomy has also been reported for CARD9 and CYBA 68,69 . However, LRBA showed the largest isodisomy at approximately 1 Mb 22 .…”

Section: Discussionmentioning

confidence: 62%

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Analysis of LRBA pathogenic variants and the association with functional protein domains and clinical presentation

Perez‐Perez,

Santos‐Argumedo,

Rodriguez‐Alba

et al. 2024

Pediatric Allergy Immunology

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LRBA is a cytoplasmic protein that is ubiquitously distributed. Almost all LRBA domains have a scaffolding function. In 2012, it was reported that homozygous variants in LRBA are associated with early‐onset hypogammaglobulinemia. Since its discovery, more than 100 pathogenic variants have been reported. This review focuses on the variants reported in LRBA and their possible associations with clinical phenotypes. In this work LRBA deficiency cases reported more than 11 years ago have been revised. A database was constructed to analyze the type of variants, age at onset, clinical diagnosis, infections, autoimmune diseases, and cellular and immunoglobulin levels. The review of cases from 2012 to 2023 showed that LRBA deficiency was commonly diagnosed in patients with a clinical diagnosis of Common Variable Immunodeficiency, followed by enteropathy, neonatal diabetes mellitus, ALPS, and X‐linked‐like syndrome. Most cases show early onset of presentation at <6 years of age. Most cases lack protein expression, whereas hypogammaglobulinemia is observed in half of the cases, and IgG and IgA levels are isotypes reported at low levels. Patients with elevated IgG levels exhibited more than one autoimmune manifestation. Patients carrying pathogenic variants leading to a premature stop codon show a severe phenotype as they have an earlier onset of disease presentation, severe autoimmune manifestations, premature death, and low B cells and regulatory T cell levels. Missense variants were more common in patients with low IgG levels and cytopenia. This work lead to the conclusion that the type of variant in LRBA has association with disease severity, which leads to a premature stop codon being the ones that correlates with severe disease.

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Section: Discussionmentioning

confidence: 62%

“…Uniparental isodisomy has also been reported for CARD9 and CYBA. 68,69 However, LRBA showed the largest isodisomy at approximately 1 Mb. 22 Only one case of a heterozygous missense variant associated with irritable bowel disease has been reported.…”

Section: Discussionmentioning

confidence: 95%

Analysis of LRBA pathogenic variants and the association with functional protein domains and clinical presentation

Perez‐Perez,

Santos‐Argumedo,

Rodriguez‐Alba

et al. 2024

Pediatric Allergy Immunology

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“…Several abnormal conditions in chromosome rearrangement may result in uniparental isodisomy, while structural or numerical aberrations of chromosomes at meiosis and post-zygotic stage might lead to uniparental heterodisomy [4]. UPD might result in clinical symptoms due to the expressions of recessive genes [5], or changes in genomic imprinting [6]. However, a person might also have totally normal phenotype with UPD [7].…”

Section: Introductionmentioning

confidence: 99%

Genetic and chromosomal variation-caused inconsistencies in two parental tests

et al. 2019

Forensic Science International: Genetics Supplement Series

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Two special cases were reported where inconsistency between children and the fathers were observed at FGA locus. Regular additional STR tests were performed and no more inconsistency was observed in the first case. Through the following TA cloning and sequencing, the first case turned to be a two-step mutation between child and father. In the second case, however, one more inconsistency was found in the additional test at D4S2366, which was on Chr. 4 as well. Then, seven randomly selected STR-loci on Chromosome 4 were analyzed, indicating a possible maternal uniparental disomy (UPD) in the child with normal phenotype. This study emphasizes gene or chromosomal variations may mislead parentage test, especially variations like UPD that are relatively unfamiliar to investigators. If all the inconsistent loci are on the same chromosome, investigators should take UPD into consideration, and further tests, like chromosomal-specific STR-typing, should be applied to prevent pseudo-exclusions.

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