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- Background: The prevalence of atopic disease, which consists of conditions such as atopic dermatitis, allergies, and asthma, has been on the rise in recent decades. In children, atopic dermatitis often acts as an initial manifestation of atopic disease and frequently precedes the development of food allergies, asthma, and allergic rhinitis. Mutations in the FLG gene, encoding the fillagrin precursor profillagrin, serve as a genetic risk factor for these diseases. Approximately 25%–50% of individuals with atopic dermatitis carry FLG mutations. It has been proposed that FLG mutations exhibit variations specific to different populations, indicating distinct patterns within each population.Severe allergic symptoms could indicate the presence of an underlying immunodeficiency or immune dysregulation and in patients with severe, early-onset, or simultaneous allergic conditions, these could be suggestive of an underlying Primary Atopic Disorder. Specifically, the allergic triad characterized by elevated IgE levels, eosinophilia, and eczema is a common feature in various inborn errors of immunity that could be mistakenly diagnosed as severe allergic conditions.Method: Our patient’s medical record was analyzed retrospectively, including her medical history, as well as results from immune laboratory tests and genetic analyses.Results: We present a 9-year-old female of mixed ethnicity with a history severe eczematous rash diagnosed with atopic dermatitis. Whole exome sequencing analysis revealed an initially novel heterozygous variant in the FLG gene (NM_002016: EXON3:c.C2218T: p.R740X).Conclusion: Healthcare providers caring for patients with atopic dermatitis and recurrent staphlococcus infections should be aware of the significant link between filaggrin gene mutations and the development of severe, persistent atopic dermatitis that begins in childhood, as well as its association with recurring staphlococcus infections. Additionally, they should keep in mind that certain inborn errors of immunity may predominantly manifest as severe and treatment-resistant atopic disorders.Statement of novelty: We have identified a rare variant in the FLG gene associated with severe atopic dermatitis and allergies.
- OPEN ACCESSBackground: X-linked severe combined immunodeficiency (SCID) is caused by mutations in the IL2RG gene and classically presents with absent T cells and natural killer (NK) cells. Mutational analysis has contributed to the understanding of this gene.Methods: The primary immunodeficiency (PID) registry was reviewed for patients with SCID with novel IL2RG mutations. The clinical phenotype was assessed using a retrospective chart review.Results: We describe 3 novel mutations in the IL2RG. The first was a guanine to adenine substitution at position 215 (c.215 G > A) in exon 2 leading to a cysteine to tyrosine substitution at position 72 (p.Cys72Tyr), with a typical T− B+ NK− phenotype. The second was a deletion of thymine at position 618 and adenine at position 619 (c.618_619TA) in exon 5, leading to a frameshift at the 206 amino acid (p.His206fs). The phenotype was characterized by a classic SCID presentation and immunophenotyping revealed a low number of absolute lymphocytes with mostly B cells, low levels of immunoglobulins, as well as very low NK cells. Finally, the third mutation was a guanine to cytosine substitution at position 341 (c.341 G > C) in exon 3 leading to a glycine to alanine substitution at position 114 (p.Gly114Ala), presenting with a T+ B+ NK+ phenotype. The presence of T and NK cells in IL2RG are discussed in the context of other mutations allowing for T and NK cells in IL2RG mutations, as well as in the setting of maternal engraftment.Conclusion: To the best of our knowledge we describe 3 novel mutations in the IL2RG gene and the associated phenotypes. These mutations illustrate that these patients can have atypical immunological evaluations.Statement of novelty: To the best of our knowledge, this paper describes 3 novel mutations in the IL2RG gene.
