The effects of melatonin and metformin on histological characteristics of the ovary and uterus in letrozole-induced polycystic ovarian syndrome mice: A stereological study

Background: Polycystic ovarian syndrome (PCOS) with anovulation, hyperandrogenism, ovarian and uterine histological changes, menstrual irregularities, etc. signs is an infertility type. It seems that melatonin and metformin can improve these abnormalities. Objective: To evaluate the effects of melatonin and metformin on the ovary and uterus in PCOS-induced mice using stereological methods. Materials and Methods: Seventy-two adult female BALB/c mice (8-wk-old, 20-30 gr) were randomly divided into control (distilled water, gavage), PCOS (90 μg/kg letrozole, gavage), PCOS+metformin (500 mg/kg, gavage), PCOS+melatonin (10 mg/kg, intraperitoneal injection), and PCOS+melatonin control (0.5% ethanol saline) groups (n = 12/each). Another PCOS group was kept for a month to ensure that PCOS features remained. Finally, a stereological evaluation of the uterus and ovary was carried out, and vaginal cytology and serum testosterone levels were assessed. Results: PCOS mice treated with metformin and melatonin had lower testosterone levels, body weight, and more regular estrus cycles than the PCOS group (p ≤ 0.001). A significant decrease in conglomerate and daughter gland numbers, and primary, secondary, atretic, and cystic follicles numbers with a significant increase in primordial and Graafian follicles, and corpus luteum numbers (p ≤ 0.001) was seen in these treated mice. Also, endometrial vessels’ volume and length significantly increased, but ovarian, endometrial, myometrial, stromal, and glands volume, and endometrial and myometrial thickness dramatically declined (p ≤ 0.001). Conclusion: It appears that metformin and melatonin could restore the PCOS phenotype including estrus cycle irregularity, high testosterone level, and ovarian and uterine micromorphology to the control levels. However, the 2 treatments had similar effects on the examined parameters. Key words: Polycystic ovarian syndrome, Melatonin, Metformin, Ovary, Uterus, Mice, Stereology

Molecular genetic characterisation of the flm genes of Aeromonas caviae

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Mental retardation due to chromosomal translocation in an Iranian consanguineous family: report of three cases

Background: Mental retardation is defined as impaired mental capacity and ability to comply with environmental and social conditions. Chromosomal abnormalities are the most important causes of mental retardation. Carriers of balanced chromosomal translocation are phenotypically normal, although they may be at risk of infertility, recurrent miscarriage or giving birth to mentally retarded children. These abnormalities are caused because chromosomes participated in the reciprocal translocations produce quadrivalents at meiosis. These quadrivalents segregate and lead to several different meiotic outcomes, just two of which are normal or balanced. Case Presentation: A consanguineous family with three mentally retarded daughters at the ages of 24, 18 and 10 years was referred to Comprehensive Medical Genetics Centre, Shiraz, Iran in 2015. Family history showed a case of unexplained infant death as well as a spontaneous abortion. Three survived siblings had hypotonia and severe developmental delay during infantile period. In addition, they suffer from primary amenorrhea. Two siblings have vesicoureteral reflux (VUR). Cytogenetic analysis of two patients showed 46,XX,t(6;12)(q23;q22),der(9)t(8;9)(q24;p24) with partial monosomy of chromosome 9 and partial trisomy of 8q24 segment, while the other patient had 46,XX,der(12)t(6;12)(q23;q22) with partial monosomy of 12q22qter and partial trisomy of 6q23qter segment. Their mother had two balanced chromosomal translocations (46, XX, t(6,12)(q21;q22), t(8,9)(q24;p24)). Conclusion: The above presented case is another example for the rare occurrence of double balanced chromosomal translocations in a phenotypically normal person. Although the most important causes of mental retardation in consanguineous marriages are autosomal recessive disorders, the role of chromosomal aberrations in mental retardation in these families must not be neglected. In other words, cytogenetic studies should be performed as a first line test in either situation

Autosomal recessive polycystic kidney disorder due to two novel compound heterozygote mutations in PKHD1 gene: case report

Background: Autosomal recessive polycystic kidney disorder (ARPCKD) is one of the most prevalent hereditary disorders in neonates and children. Its frequency is between 1/6000 to 1/55000 births. In the most severe cases, it can be diagnosed prenatally by the presence of enlarged, echogenic kidneys and oligohydramnios. However, in the milder forms, clinical manifestations are usually detected in neonatal and childhood period. PKHD1 gene located on chromosome 6 is linked with this disorder. About half of detected mutations in this gene are missense ones. The largest protein product of this gene is called the FPC/polyductin complex (FPC). It is a single-membrane spanning protein whose absence leads to abnormal ciliogenesis in the kidneys. Case presentation: Here we present a 5-year-old female patient affected with ARPCKD. She has been born to a non-consanguineous healthy Iranian parents. No similar disorder has been seen in the family. Prenatal history has been normal. In order to find the genetic background, DNA was extracted from patient's peripheral blood lymphocytes. PKHD1 gene exons and exon-intron boundaries were sequenced using next generation sequencing platform. Two novel variants have been detected in compound heterozygote state in the patient (c.6591C>A, c.8222C>A). Bioinformatics tools predicted these variants to be pathogenic. Conclusion: In the present study, we detected two novel variants in PKHD1 gene in a patient with ARPCKD. The relatively mild phenotype of this patient is in accordance with the missense mutations found. Molecular genetic tools can help in accurate risk assessment as well as precise genotype-phenotype correlation establishment in families affected with such disorder to decrease the birth of affected individuals through preimplantation genetic diagnosis or better management of disorder

A CDH3 Mutation is Segregated in an Iranian Family with Congenital Hypotrichosis and Juvenile Macular Dystrophy

Backgrounds Hypotrichosis with juvenile macular dystrophy (HJMD) is a rare genetic disorder caused from mutations in the Cadherin 3 (CDH3) gene. Results In the present study, we reported an Iranian family with three affected members born to a consanguineous parent. Mutational analysis using whole exome sequencing has revealed a nucleotide change in CDH3 gene (NM_001793:exon8:c.830delG) which leads to a frame-shift mutation (p.G277Afs*20). No intra-familial phenotypic variation was found. Conclusion Identification of disease-causing mutation in this family facilitated the effective genetic counseling and prenatal diagnosis

Evaluation of Genome in Early Familial Coronary Artery Disease: A Case Report

Background and Objectives: Coronary artery diseases (CAD) are the most common cause of death in Iran and worldwide. Myocardial infarction (MI) is a complex multifactorial and the most severe type of CAD. Early onset MI in first degree relatives could be considered as an independent risk factor for CAD. This study was performed to investigate the genetic cause of early onset familial CAD.   Case Report: The patient was a 49-year-old female, who had an acute MI at the age of 45. Evaluation of family history indicated that her father, older brother, aunts, and male cousin were also diagnosed to have MI, and had not any diagnostic criteria for familial hypercholesterolemia, diabetes, obesity, and also they did not use alcohol and tobacco. The c.6241C>T (p.Arg2081Trp) mutation was identified in ABCA1 gene in heterozygous state (CT) in proband using Whole Exome Sequencing. Mutation was confirmed by PCR and Sanger sequencing. This mutation in heterozygous state was found in all patients and not in others. This findings show that ABCA1 gene could be a possible cause of early onset familial CAD

Splicing defect in FKBP10 gene causes autosomal recessive osteogenesis imperfecta disease: a case report

Abstract Background Osteogenesis imperfecta (OI) is a group of connective tissue disorder caused by mutations of genes involved in the production of collagen and its supporting proteins. Although the majority of reported OI variants are in COL1A1 and COL1A2 genes, recent reports have shown problems in other non-collagenous genes involved in the post translational modifications, folding and transport, transcription and proliferation of osteoblasts, bone mineralization, and cell signaling. Up to now, 17 types of OI have been reported in which types I to IV are the most frequent cases with autosomal dominant pattern of inheritance. Case Presentation Here we report an 8- year- old boy with OI who has had multiple fractures since birth and now he is wheelchair-dependent. To identify genetic cause of OI in our patient, whole exome sequencing (WES) was carried out and it revealed a novel deleterious homozygote splice acceptor site mutation (c.1257-2A > G, IVS7-2A > G) in FKBP10 gene in the patient. Then, the identified mutation was confirmed using Sanger sequencing in the proband as homozygous and in his parents as heterozygous, indicating its autosomal recessive pattern of inheritance. In addition, we performed RT-PCR on RNA transcripts originated from skin fibroblast of the proband to analyze the functional effect of the mutation on splicing pattern of FKBP10 gene and it showed skipping of the exon 8 of this gene. Moreover, Real-Time PCR was carried out to quantify the expression level of FKBP10 in the proband and his family members in which it revealed nearly the full decrease in the level of FKBP10 expression in the proband and around 75% decrease in its level in the carriers of the mutation, strongly suggesting the pathogenicity of the mutation. Conclusions Our study identified, for the first time, a private pathogenic splice site mutation in FKBP10 gene and further prove the involvement of this gene in the rare cases of autosomal recessive OI type XI with distinguished clinical manifestations

Relation of red blood cell\\\'s folate and methylenetetrahedrofolate reductase C677T polymorphism to colorectal adenoma

Background: Red Blood Cell's (RBC)’s folate may be related to decreased risk of colorectal adenoma. Methylenetetrahydrofolate reductase (MTHFR) is a key regulatory enzyme in folate metabolism. The MTHFR C677T polymorphism is located in the Exon 4 region and is associated with the change of folate level. This study evaluated the associations between RBC’s Folate levels and colorectal adenoma risk, taking into account whether this associations is modified by MTHFR Polymorphism. Methods: In a case-control study conducted from January to October 2007 in Endoscopy-Colonoscopy ward of Shahid Faghihi Hospital, Shiraz. Participants were 177 case of colorectal adenoma who had pathologic-confirmed adenomatous polyps in full colonoscopy examination and 366 controls without polyps in full colonoscopy. Fasting venous blood were drawn from patients in order to determine RBC’s folate and to identify the MTHFR polymorphism by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Results: Gender Distribution in the patient group were 57.6% male and 42.3% female and control group consisted of 55.1% male and 43.9% female. 50.2% of cases and 49.2% of controls were in the age group “45 years and above”. The T allele frequency was 56.6% in control group and 34.4% in colorectal adenoma patients. There was a significant association between T allele in -677 position of MTHFR gene and colorectal adenoma susceptibility (OR: 1.85, 95% CI: 0.76-4.24, P0.05) but mean concentration of RBC’s folate was the lowest in TT genotype compare with two other genotype. Odd's Ratio for low (<140ng/ml) versus high level of RBC’s folate in participants with TT genotype was (OR: 2.08, 95% CI: 0.10-2.19, P<0.05) as compare with the CC ones. Conclusion: The result of this study suggested an inverse association between RBC's folate concentration and colorectal adenomas risk, which may be more relevant for those with the MTHFR TT genotype

The First Case of a Small Supernumerary Marker Chromosome 18 in a Klinefelter Fetus: A Case Report

Small supernumerary marker chromosomes (sSMCs), or markers, are abnormal chromosomal fragments that can be hereditary or de novo. Despite the importance of sSMCs diagnosis, de novo sSMCs are rarely detected during the prenatal diagnosis process. Usually, prenatally diagnosed de novo sSMCs cannot be correlated with a particular phenotype without knowing their chromosomal origin and content; therefore, molecular cytogenetic techniques are applied to achieve this goal. The present study aimed to characterize an sSMC in a case of Klinefelter syndrome using an in-house microsatellite analysis method and fluorescent in situ hybridization (FISH) technique. Amniotic fluid was collected from a pregnant woman who was considered to have risk factors for trisomy higher than the screening cut-off. Karyotype analysis was followed by the amplification of different microsatellite loci and FISH technique. Karyotype analysis identified a fetus with an extra X chromosome and also an sSMC with unknown identity. Further investigation of the parents showed that the sSMC is de novo. Microsatellite amplification by quantitative fluorescent PCR (QF-PCR) and FISH analysis showed that the sSMC is a derivative of chromosome 18. Eventually, the patient decided to terminate the pregnancy. Here, the first case of the coincidence of sSMC 18 in a Klinefelter fetus is reported