Background/Objectives Atopic dermatitis (AD) is the most prevalent inflammatory skin disorder, and is often associated with a personal or family history of atopic disease. The presence of loss‐of‐function mutations in the filaggrin gene (FLG) is the main predisposing factor for AD FLG mutations show ethnic and geographical variations, even between European populations. We sought to determine the frequency of the 3 most common FLG null mutations in a population of Spanish children consisting of healthy controls and AD patients. We also investigated the association between these 3 FLG mutations and AD. Methods A total of 214 participants (111 AD patients and 103 healthy controls) were enrolled in this study. Genotyping for 3 FLG null mutations (R501X, 2282del4, and R2447X) was performed by conventional Sanger sequencing. Results The combined mutation frequency was 1.9% in the control group and 12.6% in the AD group. The most common FLG mutation in AD patients was R501X (9.9%), followed by R2447X (2.7%) and 2282del4 (1.8%). Conclusion These findings further our understanding of the prevalence of FLG null mutations in the Spanish population, and suggest that the frequency of FLG mutations in AD patients in Spain is slightly higher than that of other Mediterranean countries.

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Background Atopic dermatitis (AD) is the most prevalent inflammatory skin disorder, characterized by impaired epidermal barrier function and an altered immune response, both of which are influenced by vitamin D deficiency. Single-nucleotide polymorphisms (SNPs) in VDR and CYP24A1 have been previously associated with AD. Objective We sought to characterize the associations between the VDR and CYP24A1 polymorphisms and the vitamin D and lipid biochemical profile in children diagnosed with AD. Methods A total of 246 participants (143 patients with AD and 103 healthy controls) were enrolled in this study. Genotyping for polymorphisms in VDR (rs2239185, rs1544410, rs7975232, rs2238136, rs3782905, rs2239179, rs1540339, rs2107301, rs2239182, and rs731236) and CYP24A1 (rs2248359 and rs2296241) was performed by allele-specific polymerase chain reaction using integrated fluidic circuit technology. Serum levels of calcium, phosphorus, and vitamin D were measured, and the biochemical lipid profile was determined. Results Among VDR SNPs, rs2239182 exerted a protective effect against the development of AD, whereas rs2238136 was identified as a risk factor for AD. The GCC haplotype (rs2239185-G, rs1540339-C, and rs2238136-C) appeared to protect against the development of AD. rs2239182-CC was associated with higher 25(OH)D concentrations, whereas rs2238136-TT, rs2239185-GA, and rs2248359-TT were present in a large proportion of patients with serum vitamin D deficiency. rs2239185-AA, rs2239182-CC, and rs1540339-CC were associated with higher serum total cholesterol; rs2239182-TT was associated with lower low-density lipoprotein cholesterol; and rs2239182-TC with lower high-density lipoprotein cholesterol. Both CYP24A1 SNPs (rs2296241-AA and rs2248359-TT) were associated with higher high-density lipoprotein cholesterol levels. Conclusions The VDR SNP rs2238136 is a risk factor for AD and other SNPs in VDR and CYP24A1, which may lead to alterations in biochemical parameters that influence the risk of AD. Our findings highlight the complex genetic basis to AD and indicate that interrelationships between different genetic factors can lead to alterations in vitamin D metabolism or lipid profiles, which in turn may influence the development of AD.

Background Lamb–Shaffer syndrome (LAMSHF) is a rare neurodevelopmental disorder caused by heterozygous mutation or microdeletion involving the SOX5 gene. LAMSHF is characterize by developmental delay, intellectual disability, poor expressive speech, mild dysmorphic facial features and skeletal abnormalities. Case presentation We presented a case of a child with delayed psychomotor development in all areas, scoliosis, peculiar facies, and suspicion of intermittent endotropia, alteration in the alignment of one foot and difficulty in standing. These clinical features lead to genetics studies, in which a novel pathogenic variant in the SOX5 gene was detected in association with LAMSHF. Conclusions LAMSHF should be suspected in patients with developmental delay, speech delay, intellectual disability, behavioural disturbances, ophthalmological alterations and skeletal abnormalities. A novel pathogenic mutation in the SOX5 gene c.1627del p.(Tyr543IlefsTer14) was identified in this patient as responsible of Lamb–Shaffer syndrome. This case contributes to understanding the genetic characteristics, clinical features, and diagnosis of LAMSHF.

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