Case report: Filamin A mutation lung disease recognized in an eleven-year-old child

The loss of function due to mutations in the Filamin A (FLNA) gene may result in abnormality of the filamin A protein. Of the many clinical syndromes, this condition may produce chronic lung disease, which usually presents and is diagnosed in the infant/toddler age group. Its clinical pattern may mimic broncho-pulmonary dysplasia . It is part of the entities included in Childhood Interstitial Lung Disease (chILD) group of disorders . We are herein reporting a patient that was diagnosed with FLNA-associated lung disease at eleven years of age. This case provides a unique insight into the long-term course of lung disease in this illness and broadens our understanding of the spectrum of its presentation. Although the patient had symptoms early in life, the diagnosis was not entertained because of the rarity of the disorder, its atypical and clinically mild presentation, and discontinuous care due to parents moving to different cities for employment reasons. Her presentation to our institution was for pneumonia. Due to highly unusual chest x-ray images, asthenia, and early clubbing, an extensive work up included further imaging and a lung biopsy. The final diagnosis was confirmed by the detection of FLNA loss of function (LOF) gene mutation. This article is protected by copyright. All rights reserved

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Letter to the editor

Stratified analyses refine association between TLR7 rare variants and severe COVID-19

Summary: Despite extensive global research into genetic predisposition for severe COVID-19, knowledge on the role of rare host genetic variants and their relation to other risk factors remains limited. Here, 52 genes with prior etiological evidence were sequenced in 1,772 severe COVID-19 cases and 5,347 population-based controls from Spain/Italy. Rare deleterious TLR7 variants were present in 2.4% of young (<60 years) cases with no reported clinical risk factors (n = 378), compared to 0.24% of controls (odds ratio [OR] = 12.3, p = 1.27 × 10−10). Incorporation of the results of either functional assays or protein modeling led to a pronounced increase in effect size (ORmax = 46.5, p = 1.74 × 10−15). Association signals for the X-chromosomal gene TLR7 were also detected in the female-only subgroup, suggesting the existence of additional mechanisms beyond X-linked recessive inheritance in males. Additionally, supporting evidence was generated for a contribution to severe COVID-19 of the previously implicated genes IFNAR2, IFIH1, and TBK1. Our results refine the genetic contribution of rare TLR7 variants to severe COVID-19 and strengthen evidence for the etiological relevance of genes in the interferon signaling pathway