Clinical and genetic heterogeneity in monogenetic disorders represents a major diagnostic challenge. Although the presence of particular clinical features may aid in identifying a specific cause in some cases, the majority of patients remain undiagnosed. Here, we investigated the utility of whole-exome sequencing as a diagnostic approach for establishing a molecular diagnosis in a highly heterogeneous group of patients with varied intellectual disability and microcephaly. Whole-exome sequencing was performed in 38 patients, including three sib-pairs, in addition to or in parallel with genetic analyses that were performed during the diagnostic work-up of the study participants. In ten out of these 35 families (29 %), we found mutations in genes already known to be related to a disorder in which microcephaly is a main feature. Two unrelated patients had mutations in the ASPM gene. In seven other patients we found mutations in RAB3GAP1, RNASEH2B, KIF11, ERCC8, CASK, DYRK1A and BRCA2. In one of the sib-pairs, mutations were found in the RTTN gene. Mutations were present in seven out of our ten families with an established etiological diagnosis with recessive inheritance. We demonstrate that whole-exome sequencing is a powerful tool for the diagnostic evaluation of patients with highly heterogeneous neurodevelopmental disorders such as intellectual disability with microcephaly. Our results confirm that autosomal recessive disorders are highly prevalent among patients with microcephaly.

Cadmium (Cd) as a heavy metal damages testis and decreases fertility, however, antioxidants can improve sperm parameters and decrease male infertility. In this study we investigated the effect of astaxanthin (AST) on sperm parameters, expression levels of CatSper1 and CatSper2 genes in presence of Cd in mice. Thirty adults’ mice were divided into 4 groups, sham group received olive oil and saline (olive oil is the solvent of AST and saline is the solvent of Cd), Cd group received 1 mg/kg Cdcl₂, a group received 10 mg/kg AST and 1 mg/kg Cdcl₂ and a group received 10 mg/kg AST. The treatments were done intraperitoneally for 14 days. After 14 days sperm parameters were analyzed. Malondialdehyde level, catalase enzyme activity, the alteration of CatSper1 and CatSper2 genes expression were measured in testis. Results showed that Sperm count, viability, CatSper1 gene expression and catalase activity significantly decreased by Cd compared to sham group. Cd significantly increased sperm DNA fragmentation (SDF), abnormal sperm morphology and malondialdehyd level compared to sham group. AST significantly increased sperm count, viability and CatSper1 gene expression and decreased SDF and abnormal sperm in comparison with Cd group. AST protected testis and decreased oxidative stress induced by Cd. Our findings indicated that AST could protect sperm DNA, enhanced CatSper1 gene expression and sperm quality in presence of Cd. No significant differences were found in CatSper2 expression among treatments. Therefore, AST as a strong antioxidant can help to protect the potential of fertility against Cd toxicity. Received: 09 April 2021 Received: 11 July 2021 Accepted: 12 July 2021 Publication Date: 18 August 2021 (online) © 2021. Thieme. All rights reserved. Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

The effects of Vanillic Acid (VA) on germination, seedling and adult plant of rice (Oryza sativa L.) were investigated. Four cultivars, traditional (Taroom mahalli and Taroom deilamani) and improved (Shafagh and Onda) were studied. For germination, seeds were sterilized and then placed on Petri dish at 30 degrees C at different concentrations (0, 10, 20 and 25 mM) for 7 days and growth factors of seedling were measured after 14 days. Seedling (10 days) planted in hydroponic medium including nutrient solution amended with 0, 25, 50 and 100 mg kg(-1) VA. After 30 days, the growth factors were determined, alpha-amylase and peroxidase activities were assayed by Bernfeld and Maehly methods, respectively. Present results indicated that as a result of increasing concentrations of VA, germination percentage and germination rate as well as alpha-amylase activity markedly decreased except Onda in all cultivars. In all cultivars, seedling growth factors such as shoot length, fresh weight and dry weight as well as root have been reduced by increasing of VA. In adult plant, also shoot length, root length, shoot dry weight and root fresh weight were reduced by increasing concentrations of VA. Shoot fresh weight was decreased in Shafagh by increasing concentrations of VA; meanwhile, we have not observed any significant differences in the other cultivars. In the case of root dry weight, there were not significant differences in any cultivars. With increasing concentrations of VA, chlorophyll content reduced; on the contrary, peroxidase activity increased.