Investigation of the molecular genetic causes of non-syndromic primary ovarian insufficiency by next generation sequencing analysis.

Objective: The aim of this study is to investigate the molecular genetic causes of non-syndromic primary ovarian insufficiency (POI) cases with the gene panel basedon next generation sequencing analysis and to establish the relationship between genotype and phenotype. Materials and methods: Twenty three cases aged 14-40 years followed up with POI were included. Patients with a karyotype of 46, XX, primary or secondary amenorrhea before the age of 40, with elevated FSH (>40 IU/mL) and low AMH levels (<0.03 ng/mL) were included in the study. Molecular genetic analyzes were performed by the next generation sequencing analysis method targeted with the TruSight TM Exome panel. Results: Median age of the cases was 17.8 (14.0-24.3) years, and 12 (52%) cases admitted before the age of 18. Fifteen (65%) patients had consanguineous parents. In2 (8.6%) cases, variants detected were in genes that have been previously proven to cause POI. One was homozygous variant in FIGLA gene and the other was homozygous variant in PSMC3IP gene. Heterozygous variants were detected in PROK2, WDR11 and CHD7 associated with hypogonadotropic hypogonadism, but these variants are insufficient to contribute to the POI phenotype. Conclusion: Genetic panels based on next generation sequencing analysis technologies can be used to determine the molecular genetic diagnosis of POI, which has a highly heterogeneous genetic basis.

Does the TMPRSS6 C > T Polymorphism Modify the Endurance Training Effects on Hematological Parameters?

This study investigated the role of TMPRSS6 C > T polymorphism (TMPRP) on the effects of chronic aerobic training on main hematological parameters in male soccer referees, which is yet unknown. Two groups composed of total of 45 healthy male soccer referees and 42 sedentary were compared for hemogram, serum hepcidin, ferritin, and iron levels. TMPRP was determined from genomic DNA samples. Participants' physical and physiological (Yoyo endurance level-2 test) measurements were carried out. The athletic T carrier (Tc = TT + TC) group RBC count was significantly higher than the control (p < 0.01), whereas the athletic CC homozygous group serum iron and transferrin saturation (TS) were lower than the control depending on the TMPRP. The ferritin and iron values of the athletic Tc group were higher than of the athletic CC group (29.2% and 14.1%, respectively; p > 0.05) although the control Tc group RBC (p < 0.05) and iron (23.8%, p > 0.05) values were lower than the control CC due to genetic tendency. The training did not change hepcidin levels. These results suggest that the TMPRP can modify the endurance training effects on iron and TS levels and RBC count (in the CC and Tc groups) respectively. The CC group may be adversely affected for iron and TS from endurance trainings. It may be recommended that the training programs should be organized according to phenotype characteristics.

Analysis of the alpha galactosidase gene: mutation profile and description of two novel mutations with extensive literature review in Turkish population.

Objectives Fabry disease (FD, OMIM #301500) is a rare and progressive X-linked lysosomal storage disorder. FD is caused by mutations in the GLA gene on chromosome Xq22. Methods In this article, we aimed to present the largest sample of GLA mutation spectrum including common and novel variants in Turkish population. GLA gene sequence analysis was performed on the subjects who applied to the department of medical genetics with the preliminary diagnosis of FD between 2013 and 2018. Results We detected 22 different mutations as two novel [(p.F69S(c.206T>C), p.P205A (c.613C>G)] and 20 previously reported GLA mutations in 47 individuals from 22 unrelated families. These mutations included 14 missense mutations, four nonsense mutations, two small deletions, one small deletion/insertion and one small insertion. Major clinical findings of the female case with p.F69S(c.206T>C) mutation were cornea verticillata, acroparesthesia, angiokeratoma, psychiatric and gastrointestinal symptoms. Other novel mutation (p.P205A [c.613C>G]) was carried by a male case presenting gastrointestinal symptoms. Conclusions We described clinical findings of two cases that had novel mutations to provide more insight in genotype-phenotype correlation. We presented the largest mutation spectrum in Turkish population and reviewed previous mutations in this article.

The effects of regular aerobic exercise training on blood nitric oxide levels and oxidized LDL and the role of eNOS intron 4a/b polymorphism.

BACKGROUND: Nitric oxide (NO), oxidized LDL (OxLDL) and endothelial nitric oxide synthase intron 4a/b polymorphism (eNOSP) are related to atherosclerosis (AS). The present study investigated the effects of regular aerobic exercise training on the mentioned risk factors as well as blood lipids and lipoproteins (BLLPs) and the role of eNOSP, which is unclear. METHODS: The study was participated by 46 well trained male soccer referees as the athletic group (AG, age; 23.26 ± 2.84 years) and 43 sedentary controls (CG, age; 23.16 ± 3.28 years). Yoyo intermittent endurance (Yoyo IE-2 test) was performed to measure aerobic endurance levels of the participants. Serum NO, eNOS and oxidized LDL (OxLDL) levels (by ELISA method) and total oxidant /antioxidant status ratio (/TOS/TAS) as oxidative stress (OS) index (OSI) and BLLPs levels were determined. eNOSP was identified from genomic DNA samples with VNTR analysis. RESULTS: There is no significant difference between AG and CG including the genotype groups for NO, eNOS and BLLPs and eNOSP has no role. However, AG's NO (29%, p > .05) and TAS levels were significantly higher (p = .001) than those of CG, whereas OSI (p = .001) and OxLDL (p = .011) values were significantly lower. On the other hand, NO value of the athletic bb group was 29% higher compared with the control and the a carrier (aC = aa + ab) group. CONCLUSIONS: These findings suggest that regular aerobic exercise improves blood NO levels and antioxidant capacity, while decreasing OS levels including OxLDL, but not eNOS and BLLPs in the athletes. Although the polymorphism does not have a modifying effect on these effects, bb genotype group may benefit more from training for NO than aC group due to genetic tendency.