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.

Resumen Objetivos La distrofia miotónica tipo 1, conocida también como enfermedad de Steinert, es un desorden multisistémico crónico, degenerativo e incapacitante de expresividad clínica muy variable provocado por una expansión heredada de manera autosómica dominante de la repetición del triplete citosina-timina-guanina, localizada en la región 3′ no codificante del gen DMPK (19q13.3). Caso clínico En este estudio, presentamos el caso de una familia con varias expansiones de la repetición CTG intergeneracionales, con un caso adicional de falsa sospecha de fenómeno de contracción, debido a las limitaciones de la técnica TP-PCR. Conclusiones La inestabilidad meiótica de las repeticiones de (CTG)n provoca anticipación genética. De este modo, a lo largo de las sucesivas generaciones, se ha hallado un incremento del tamaño de la mutación DM1 y un fenotipo más severo en los individuos afectados. Aunque es extremadamente infrecuente, en la transmisión de padres a hijos, también puede producirse una disminución en el número de repeticiones de CTG, siendo esta más frecuente en la transmisión paterna.

Objectives Myotonic dystrophy type 1 (DM1), also known as Steinert’s disease, is a chronic, progressive and disabling multisystemic disorder with a broad spectrum of severity that arises from an autosomal-dominant expansion of the Cytosine-Thymine-Guanine (CTG) triplet repeat in the 3′ untranslated region of the DMPK gene (19q13.3). Case presentation In this study, we report the case of a family with several intergenerational expansions of the CTG repeat, with an additional case of a false suspicion of contraction phenomenon due to TP-PCR limitations. Conclusions The meiotic instability of the (CTG)n repeats leads to genetic anticipation where increased size of DM1 mutation and a more severe phenotype have been reported in affected individuals across generations. Even if extremely rare, a decrease in the CTG repeat size during transmission from parents to child can also occur, most frequently during paternal transmissions.

Background Waardenburg syndrome (WS) is a rare genetic disorder characterized by musculoskeletal abnormalities, deafness and hypopigmentation of hair and skin. This article’s aim is to investigate clinical and genetic characteristics of WS in three unrelated Caucasian individuals. Case presentation The first patient was a 25-year-old female with congenital bilateral hearing loss, bright-blue-eyes, hypopigmentation of hair and skin, megacolon, language retardation, tenosynovitis and neuromas. The second case was an infant symptomatic from birth, with dysphagia, Hirschsprung disease and neurological abnormalities. The third patient was a 14-year-old boy with congenital bilateral hearing loss and ileocolic Hirschsprung disease. In order to identify variants in potentially causal genes of the patients’ phenotype, genetical testing was conducted: targeted clinical exome, targeted exome and trio exome, respectively. We identified three novel variants spread throughout the coding sequence of SOX10. The c.395C>G variant identified de novo in patient 1 was a single nucleotide substitution in exon 2. The c.850G>T variant identified as heterozygous in patient 2 was a loss-of-function variant that generated a premature stop codon. The c.966dupT variant identified in patient 3 was a duplication that generated a premature stop codon. It had been identified in his father, arising a possible germinal mosaicism. According to in silico predictors the variant identified in patient 1 was considered as pathogenic, whereas the other two were classified as likely pathogenic. Conclusions An exact description of the mutations responsible for WS provides useful information to explain clinical features of WS and contributes to better genetic counselling of WS patients.

Adaptation and analytical evaluation of urinary ammonium measurement using an automated method for plasma ammonium quantification Automatización y evaluación del rendimiento de un método adaptado para la determinación del amonio urinario