Novel compound heterozygous LRBA deletions in a 6-month-old with neonatal diabetes

Sanyoura, May; Lundgrin, Erika L.; Subramanian, Hari Prasanna; Yu, Min; Sodadasi, Priscilla; Greeley, Siri Atma W.; MacLeish, Sarah A.; Gaudio, Daniela del

doi:10.1016/j.diabres.2021.108798

Cited by 6 publications

(3 citation statements)

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“…Only 29.5% of the reported cases included protein expression assays; 93% did not express LRBA, as assessed either by immunoblotting (in 96.7% of cases) or flow cytometry, and 90.2% of the patients presented with homozygous variants and were born to endogamous families. Compound heterozygous variants were found in lower percentages (11%) 46,48,60 . Finally, one case of uniparental isodisomy has been reported 22,61 .…”

Section: Resultsmentioning

confidence: 91%

“…The key terms used in the search were LRBA in HGMD, LRBA deficiency, LRBA variants, LRBA clinical presentation, and LRBA only in PubMed and Scopus. The reports spanned from 2012 to 2023 1,2,4,16–19,21–59 (Table S1). Reports that included well‐specified variants and their associated phenotypes were also included.…”

Section: Methodsmentioning

confidence: 99%

“…Compound heterozygous variants were found in lower percentages (11%). 46,48,60 Finally, one case of uniparental isodisomy has been reported. 22,61 Only one patient was reported to have a heterozygous variant 26 ; such a case is indicated in Figure S2 and Table S1.…”

Section: Variants In Lrba Cause Absence Of Protein and Predominantly ...mentioning

confidence: 99%

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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: Resultsmentioning

confidence: 91%

Section: Methodsmentioning

confidence: 99%