Updated mutational spectrum and genotype-phenotype correlations in ichthyosis patients with ABCA12 pathogenic variants.

Autosomal recessive congenital ichthyoses (ARCI) is a genetically heterogeneous condition that can be caused by pathogenic variants in at least 12 genes, including ABCA12. ARCI mainly consists of congenital ichthyosiform erythroderma (CIE), lamellar ichthyosis (LI) and harlequin ichthyosis (HI). The objective was to determine previously unreported pathogenic variants in ABCA12 and to update genotype-phenotype correlations for patients with pathogenic ABCA12 variants. Pathogenic variants in ABCA12 were detected using Sanger sequencing or a combination of Sanger sequencing and whole-exome sequencing. To verify the pathogenicity of a previously unreported large deletion and intron variant, cDNA analysis was performed using total RNA extracted from hair roots. Genetic analyses were performed on the patients with CIE, LI, HI and non-congenital ichthyosis with unusual phenotypes (NIUP), and 11 previously unreported ABCA12 variants were identified. Sequencing of cDNA confirmed the aberrant splicing of the variant ABCA12 in the patients with the previously unreported large deletion and intron variant. Our findings expand the phenotype spectrum of ichthyosis patients with ABCA12 pathogenic variants. The present missense variants in ABCA12 are considered to be heterogenous in pathogenicity, and they lead to varying disease severities in patients with ARCI and non-congenital ichthyosis with unusual phenotypes (NIUP).

Time kinetics of cyclobutane pyrimidine dimer formation by narrowband and broadband UVB irradiation.

BACKGROUND: Maximum cyclobutane pyrimidine dimer (CPD) formation in the skin induced by ultraviolet B (UVB) irradiation is thought to occur within a few minutes and is immediately decreased by the DNA repair system. OBJECTIVE: We evaluated the time course and differential effects of narrowband (NB-UVB) and broadband (BB-UVB) UVB on CPD formation. METHODS: We investigated CPD formation at various time-points in vivo, from 3 min to 72 h, after UVB irradiation using 2 mouse strains, C57BL/6 J and BALB/c. The backs of the mice were shaved and irradiated with NB-UVB or BB-UVB. Skin specimens were obtained and stained with anti-CPD antibody. Positive signals in the epidermis were measured using ImageJ. DNA was extracted from the isolated epidermis and subjected to quantitative CPD analysis by enzyme-linked immunosorbent assay (ELISA). RESULTS: CPDs induced by UVB irradiation (1 minimum erythemal dose) in epidermal skin were detected in the nucleus. Although the CPD levels increased immediately after irradiation (3 min), the highest level was detected at 1 h and the increase lasted 24-48 h after irradiation. BB-UVB tended to induce greater CPD levels than NB-UVB in both mouse strains. The ELISA showed similar results. CONCLUSIONS: CPDs were induced immediately after UV irradiation, with the maximum level observed 1 h after irradiation. BB-UVB irradiation tended to induce greater levels of CPD formation. In addition to the direct effects of UVB, the presence of CPDs in hair follicles, which were not irradiated by UVB, suggests that reactive oxygen species are also involved in CPD formation in the skin.

Circulating leptin and its muscle gene expression in Nellore cattle with divergent feed efficiency.

BACKGROUND: Leptin has a strong relation to important traits in animal production, such as carcass composition, feed intake, and reproduction. It is mainly produced by adipose cells and acts predominantly in the hypothalamus. In this study, circulating leptin and its gene expression in muscle were evaluated in two groups of young Nellore bulls with divergent feed efficiency. Individual dry matter intake (DMI) and average daily gain (ADG) of 98 Nellore bulls were evaluated in feedlot for 70 d to determinate the residual feed intake (RFI) and select 20 animals for the high feed efficient (LRFI) and 20 for the low feed efficient (HRFI) groups. Blood samples were collected on d 56 and at slaughter (80 d) to determine circulating plasma leptin. Samples of Longissimus dorsi were taken at slaughter for leptin gene expression levels. RESULTS: DMI and RFI were different between groups and LRFI animals showed less back fat and rump fat thickness, as well as less pelvic and kidney fat weight. Circulating leptin increased over time in all animals. Plasma leptin was greater in LRFI on 56 d and at slaughter (P = 0.0049). Gene expression of leptin were greater in LRFI animals (P = 0.0022) in accordance with the plasma levels. The animals of the LRFI group were leaner, ate less, and had more circulating leptin and its gene expression. CONCLUSION: These findings demonstrated that leptin plays its physiological role in young Nellore bulls, probably controlling food intake because feed efficient animals have more leptin and lower residual feed intake.