Association of FSH receptor promoter’s polymorphisms with IVF-failure in Iranian women

Background: Follicle-Stimulating Hormone Receptor (FSHR) gene shows five Single Nucleotide Polymorphisms (SNPs) in the promoter region at positions -29, -37, - 114, -123 and -138 that have been reported to be associated with higher levels of FSH and various ovarian responses to FSH in IVF (In-vitro fertilization) treatment at different populations.  Hence, they are important regulators of hormone activity at the target level in IVF process. This study was performed to investigate the association between FSHR gene polymorphisms and IVF failure in Iranian women.Methods: SNPs in the promoter region of FSHR gene were analyzed by PCR and direct sequencing technique in 90 women in three equally sized groups of IVF failure, IVF success and normal fertile women, using genomic DNA extracted from white blood cells.Results: No significant differences were found in allelic variants frequency and genotype distribution between each category of subjects when analyzing the FSHR SNPs in the promoter region (p-value >0.05).   However, analysis of the data revealed that the subjects with A/A genotype at the –29 position received higher amount of exogenous FSH for ovulation induction compared to G/G genotypes.Conclusions: These results indicate that the FSHR SNP at position –29 may influence sensitivity of the FSHR to FSH for ovulation induction in IVF treatment.  It may be concluded that the A/A genotype at position –29 is associated with poor ovarian response to FSH so that subjects with A/A genotype at the –29 position may require higher doses of exogenous FSH for ovulation induction during IVF process

Paternal age increases the risk for autism in an Iranian population sample

Background: Autism is a neurodevelopmental disorder which is known to have a strong genetic component and is most likely oligogenic. However, the necessary role of environmental factors has been well documented. Prior research suggests that parental characteristics, such as age and level of education, may be associated with a risk of autism. Parental age has been shown to be associated with many disorders, such as schizophrenia, childhood cancer and fetal death. However, results from studies of parental age and autism are inconsistent. Methods: In the present study, we investigated the association of autism with parental age in 179 autism cases and 1611 matched cohort children from Iran. Each case was matched with nine cohort controls on parental education, sex, order of birth, consanguineous marriage, urbanism and province of residence. The Cox regression model was used to carry out conditional logistic regression on the matched data. Results: There was a significant association between higher paternal age, but not maternal age, and an increasing risk of autism. An analysis of the combined effect of parental age and education also revealed that parents with higher education had an increased risk of having autistic children, with a dose-response effect of parental age. Conclusions: This study, which is the first epidemiological study of autism in Iran, provides evidence of the association of paternal age and risk of autism

MicroRNAs networks in thyroid cancers: focus on miRNAs related to the fascin

miRNAs are non coding ribonucleic acids which are protected with respect to evolution, and have a length of 18–25 nucleotides. microRNAs control the gene expression after transcription, through mRNA destruction or translation processing, and therefore participate in arrangement of the physiologic and pathologic cellular processes; They also may act as oncogene or tumor suppressors. Altered expression of a number of microRNAs is reported in process of progression and metastasis of thyroid cancers. Therefore, identification of these microRNAs may shed a light to oncogenesis pathway of thyroid cancers and their metastasis. In addition, microRNAs might apply as potential biological markers in diagnosis and treatment of thyroid cancers. The changes made in miRNAs profile of thyroid cancers are reviewed in this paper

Essential genes in thyroid cancers: focus on fascin

Although thyroid cancers are not among common malignancies, they rank as the first prevalent endocrine cancers in human. According to the results of published studies it has been shown the gradual progress from normal to the neoplastic cell in the process of tumor formation is the result of sequential genetic events. Among them we may point the mutations and rearrangements occurred in a group of proto-oncogenes, transcription factors and metastasis elements such as P53, RAS,RET,BRAF, PPARγ and Fascin. In the present article,we reviewed the most important essential genes in thyroid cancers, the role of epithelial mesenchymal transition and Fascin has been highlighted in this paper

Heterozygous De Novo Truncating Mutation of Nucleolin in an ASD Individual Disrupts Its Nucleolar Localization

Nucleolin (NCL/C23; OMIM: 164035) is a major nucleolar protein that plays a critical role in multiple processes, including ribosome assembly and maturation, chromatin decondensation, and pre-rRNA transcription. Due to its diverse functions, nucleolin has frequently been implicated in pathological processes, including cancer and viral infection. We recently identified a de novo frameshifting indel mutation of NCL, p.Gly664Glufs*70, through whole-exome sequencing of autism spectrum disorder trios. Through the transfection of constructs encoding either a wild-type human nucleolin or a mutant nucleolin with the same C-terminal sequence predicted for the autism proband, and by using co-localization with the nucleophosmin (NPM; B23) protein, we have shown that the nucleolin mutation leads to mislocalization of the NCL protein from the nucleolus to the nucleoplasm. Moreover, a construct with a nonsense mutation at the same residue, p.Gly664*, shows a very similar effect on the location of the NCL protein, thus confirming the presence of a predicted nucleolar location signal in this region of the NCL protein. Real-time fluorescence recovery experiments show significant changes in the kinetics and mobility of mutant NCL protein in the nucleoplasm of HEK293Tcells. Several other studies also report de novoNCL mutations in ASD or neurodevelopmental disorders. The altered mislocalization and dynamics of mutant NCL (p.G664Glufs*70/p.G664*) may have relevance to the etiopathlogy of NCL-related ASD and other neurodevelopmental phenotypes

Heterozygous Truncating Mutation of Nucleolin in an ASD Individual Disrupts Its Nucleolar Localization

Nucleolin (NCL/C23; OMIM: 164035) is a major nucleolar protein that plays a critical role in multiple processes, including ribosome assembly and maturation, chromatin decondensation, and pre-rRNA transcription. Due to its diverse functions, nucleolin has frequently been implicated in pathological processes, including cancer and viral infection. We recently identified a frameshifting indel mutation of , p.Gly664Glufs*70, through whole-exome sequencing of autism spectrum disorder trios. Through the transfection of constructs encoding either a wild-type human nucleolin or a mutant nucleolin with the same C-terminal sequence predicted for the autism proband, and by using co-localization with the nucleophosmin (NPM; B23) protein, we have shown that the nucleolin mutation leads to mislocalization of the NCL protein from the nucleolus to the nucleoplasm. Moreover, a construct with a nonsense mutation at the same residue, p.Gly664*, shows a very similar effect on the location of the NCL protein, thus confirming the presence of a predicted nucleolar location signal in this region of the NCL protein. Real-time fluorescence recovery experiments show significant changes in the kinetics and mobility of mutant NCL protein in the nucleoplasm of HEK293Tcells. Several other studies also report mutations in ASD or neurodevelopmental disorders. The altered mislocalization and dynamics of mutant NCL (p.G664Glufs*70/p.G664*) may have relevance to the etiopathlogy of -related ASD and other neurodevelopmental phenotypes