This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. Abstract Background: Rubinstein-Taybi syndrome (RSTS) is a rare congenital disorder characterized by broad thumbs and halluces, intellectual disability, distinctive facial features, and growth retardation. Clinical manifestations of RSTS are varied and overlap with other syndromes' phenotype, which makes clinical diagnosis challenging. CREBBP is the major causative gene (55%-60% of the cases), whereas pathogenic variants found in EP300 represent the molecular cause in 8% of RSTS patients. A wide range of CREBBP pathogenic variants have been reported so far, including point mutations (30%-50%) and large deletions (10%). Methods: The aim of this study was to characterize the CREBBP genetic variant spectrum in 39 RSTS patients using Multiplex Ligation-dependent Probe Amplification and DNA sequencing techniques (Sanger and Trio-based whole-exome sequencing). Results: We identified 15 intragenic deletions/duplications, ranging from one exon to the entire gene. As a whole, 25 de novo point variants were detected: 4 missense, 12 nonsense, 5 frameshift, and 4 splicing pathogenic variants. Three of them were classified as of uncertain significance and one of the patients carried two different variants. Conclusion: Seventeen of the 40 genetic variants detected were reported for the first time in this work contributing, thus, to expand the molecular knowledge of this complex disorder. K E Y W O R D S CREBBP, epigenetics, genotype-phenotype correlation, Rubinstein-Taybi syndrome 2 of 13 | PÉREZ-GRIJALBA Et AL.

Acute respiratory distress syndrome is a well-known complication in Plasmodium falciparum infection. It is less frequently described in Plasmodium vivax, and only one case is reported in Plasmodium ovale. Here we present the second description of this pulmonary complication in a P. ovale acute infection.

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Hereditary leiomyomatosis and renal cell cancer syndrome (HLRCC) is a very rare hereditary disorder characterized by cutaneous leiomyomas (CLMs), uterine leiomyomas (ULMs), renal cysts (RCys) and renal cell cancers (RCCs). We aimed to describe the genetics, clinical features and potential genotype-phenotype associations in the largest cohort of fumarate hydratase enzyme mutation carriers known from Spain using a multicentre, retrospective study of individuals with a genetic or clinical diagnosis of HLRCC. We collected clinical information from medical records, analysed genetic variants and looked for genotype-phenotype associations. Analyses were performed using R 3.6.0. software. We included 197 individuals: 74 index cases and 123 relatives. CLMs were diagnosed in 65% of patients, ULMs in 90% of women, RCys in 37% and RCC in 10.9%. Twenty-seven different pathogenic variants were detected, 12 (44%) of them not reported previously. Patients with missense pathogenic variants showed higher frequencies of CLMs, ULMs and RCys, than those with loss-of-function variants (p = 0.0380, p = 0.0015 and p = 0.024, respectively). This is the first report of patients with HLRCC from Spain. The frequency of RCCs was lower than those reported in the previously published series. Individuals with missense pathogenic variants had higher frequencies of CLMs, ULMs and RCys.

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