Phenotypic spectrum of autosomal recessive Keratitis-Ichthyosis-Deafness Syndrome (KIDAR) due to mutations in AP1B1.

Inborn errors in copper metabolism result in a diverse set of abnormalities such as Wilson disease and MEDNIK syndrome. Homozygous pathogenic variants in AP1B1 lead to KIDAR (Keratitis-Ichthyosis-Deafness Syndrome). The main phenotypic features of KIDAR are ichthyosis, keratitis, erythroderma, and progressive hearing loss accompanied by developmental delay and failure to thrive. Herein, we describe a six-and-a-half-year-old boy with KIDAR caused by a novel pathogenic variant in AP1B1 (NM_001127.4:c.1263C > A, p.Tyr421*). The proband presented with ichthyosis, erythroderma, palmoplantar keratoderma, hearing loss, and corneal scarring. He also had hypotonia, global developmental delay, and photophobia. Lastly, we review all of the previously reported cases and the clinical features associated with KIDAR.

Phenotype of ST3GAL3 deficient patients: A case and review of the literature.

ST3GAL3 deficiency is an extremely rare autosomal recessive disorder caused by pathogenic mutations in the ST3GAL3 gene. Epilepsy, motor development delay, severe intellectual disability, and behavioral disorders have been reported to be associated with ST3GAL3 deficiency. In the present study, ST3GAL3 deficiency was caused by a homozygous splice-site mutation (NM_174964.4: c.936+1delG) in ST3GAL3. The patient described in this study was clinically similar to previously reported cases; nevertheless, we were able to detect repetitive behavior, previously not reported manifestations.

The Effect of Bacterial Peptide p28 on Viability and Apoptosis Status of P53-null HeLa Cells.

Purpose: Despite all the efforts for discovery of efficient anti-cancer therapeutics, cancer is still a major health concern worldwide. p28 is a bacterial small peptide which has been widely investigated due to its preferential cell internalization and anti-cancer activities. Intracellularly, p28 offers its anti-cancer traits by impeding the degradation of tumor-suppressor protein "p53". In this study, we investigated the potency of p28 in inducing apoptosis or decreasing cell viability in p53-null "HeLa" cell line. Methods: The coding sequence for p28 peptide was obtained from Pseudomonas aeruginosa by PCR amplification of the p28 gene. The coding gene was cloned in pET-28a vector and transformed into E. coli bacterial host. Subsequently, the expressed peptide was purified using Ni-NTA chromatography system and introduced into the target cells. The anti-proliferative and apoptotic activity of p28 on HeLa and HEK-293 cells were investigated using MTT and PEAnnexin V Flowcytometry assays. Results: Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blotting confirmed the expression of p28 peptide in the bacterial host. Bradford assay revealed a concentration of 0.05 mg/mL for the purified p28. MTT assay of cells treated with p28 at concentrations of 0, 0.5, 1, 2 and 2.5 µM indicated 24h viability values of 97%, 89%, 88%, 87% and 84% for HeLa cells, respectively. Data obtained from flowcytometry analyses revealed 24h apoptosis rate of 7.17%, 8.05%, 8.63% and 8.84% for HeLa cells treated with 0, 0.5, 1, and 2 µM p28, respectively. Conclusion: MTT and flowcytometry apoptosis assays suggest no statistically significant effect of p28 on the viability and apoptosis status of p53-null HeLa cells when results compared to data obtained from HEK-293 cells (P>0.05). These results imply that anti-cancer efficacy of p28 is directly dependent on the presence of p53, suggesting p28 as an inappropriate therapeutic agent for treatment of cancers with negative p53 status.

The association of LRP5 (rs556442) polymorphism with body composition and obesity in postmenopausal women.

AIM: The main of this study was to investigate the association between the rs566442 (V1119V) coding polymorphism of Low-density lipoprotein receptor-related protein 5 (LRP5) with obesity and basal metabolic rate in Iranian postmenopausal women. METHODS: This cross-sectional study was performed on 350 postmenopausal women with a mean age of 57.8 years (SD ±â€¯6.14). Body composition was analyzed by bioelectrical impedance analysis (BIA) resistance. Obesity was defined based on Body mass index (BMI) ≥30 kg/m2. To determine the genotype of SNP (rs556442), PCR-RFLP assay was performed and confirmed by sequencing. DNA samples from participants were genotyped using the RFLP-PCR method. RESULTS: Among the study population 37.1% (130) were obese. G allele had minor-allele frequency of 0.38% in our population. The frequency of genotypes in our study population was 12.9% (45 person) GG, 35.7% (125 person) AA and 51.4% (180) GA. After adjusting age and menopausal age, only basal metabolic rate showed significantly higher in GG group compare to other groups (p = 0.02). Our data showed basal metabolic rate was higher in obese women with GG genotype in comparison to obese women with AG and AA genotypes. DISCUSSION: The findings of this study suggest that the GG genotype of SNP (rs556442) could protective role in obese women through the association with BMR.

Air pollution during pregnancy and placental adaptation in the levels of global DNA methylation.

BACKGROUND: Health in early life is crucial for health later in life. Exposure to air pollution during embryonic and early-life development can result in placental epigenetic modification and foetus reprogramming, which can influence disease susceptibility in later life. Objectives: The aim of this paper was to investigate the placental adaptation in the level of global DNA methylation and differential gene expression in the methylation cycle in new-borns exposed to high fine particulate matter in the foetal stage. STUDY DESIGN: This is a nested case-control study. We enrolled pregnant healthy women attending prenatal care clinics in Tehran, Iran, who were residents of selected polluted and unpolluted regions, before the 14th week of pregnancy. We calculated the regional background levels of particle mass- particles with aerodynamics diameter smaller than 2.5 µm (PM2.5) and 10 µm (PM10)-of two regions of interest. At the time of delivery, placental tissue was taken for gene expression and DNA methylation analyses. We also recorded birth outcomes (the new-born's sex, birth date, birth weight and length, head and chest circumference, gestational age, Apgar score, and level of neonatal care required). RESULTS: As regards PM2.5 and PM10 concentrations in different time windows of pregnancy, there were significantly independent positive correlations between PM10 and PM2.5 in the first trimester of all subjects and placental global DNA methylation levels (p-value = 0.01, p-value = 0.03, respectively). The gene expression analysis showed there was significant correlation between S-adenosylmethionine expression and PM2.5 (p = 0.003) and PM10 levels in the first trimester (p = 0.03). CONCLUSION: Our data showed prenatal exposures to air pollutants in the first trimester could influence placental adaptation by DNA methylation.

The impact of an educational pamphlet on the awareness of parents about 4‒6-year-old children's oral habits and dentofacial discrepancies.

Background. This study aimed to evaluate whether the parents' knowledge about the adverse effects of oral habits and dentoskeletal discrepancies would improve by an educational pamphlet. Methods. A parallel-group randomized clinical trial was conducted on parents in kindergartens of Shiraz, Iran, 2013. The parents completed a designed questionnaire to determine the pre-intervention score. The study group received an educational pamphlet on the oral habits and dentoskeletal discrepancies, in contrast to the control group. Three weeks later, the parents in both groups took the questionnaire again (post-intervention score). The primary outcome was a change in the parents' knowledge about oral habits and dentoskeletal discrepancies, which was measured by 13 questions of the questionnaire. Each correct answer was given a positive point and each incorrect answer a negative point. The total pre- and post-intervention scores were calculated by summing up the points and compared using Mann-Whitney U test. Results. A total of 550 subjects were assessed for eligibility and 413 were randomized. Of the study group, 203 subjects (98.56%), and of the control group, 204 parents (98.54%) completed the questionnaire for the second time. The score of the study group in the "normal occlusion" section of the questionnaire had significantly improved (P < 0.001) and in the "oral habits" section the score of both groups had improved but in the study group the improvement was significantly higher (P < 0.001). Conclusion . The educational pamphlet can be effective in increasing the level of parents' knowledge about normal occlusion and complications of oral habits.