A novel mutation (c.T3816 > C) in the androgen receptor gene in a 46,XY female patient with androgen insensitivity syndrome

Wstęp: Mutacje w genie receptora androgenowego (AR, Androgen Receptor) są najczęstszą przyczyną zaburzeń różnicowania płci (DSD,Disorders of Sex Development) powodującą zespół niewrażliwości na androgeny (AIS, Androgen Insensitivity Syndrome). Chorzy wykazująznaczną różnorodność fenotypu: od żeńskiego (CAIS, Complete Androgen Insensitivity syndrome) przez niecałkowicie męski (PAIS, PartialAndrogen Insensitivity Syndrome) aż do prawidłowo zbudowanych niepłodnych mężczyzn (MAIS, Mild Androgen Insensitivity Syndrome).W pracy przedstawiamy wyniki badań klinicznych, endokrynologicznych oraz molekularnych pacjentki hospitalizowanej z powodupierwotnego braku miesiączki z typowymi cechami zespołu niewrażliwości na androgeny.Materiał i metody: Celem badań było określenie podłoża molekularnego zespołu niewrażliwości na androgeny u kobiety 46,XY. Przeprowadzonoanalizę molekularną genu AR z zastosowaniem metod: MSSCP (Multitemperature Single Strand Conformation Polymorphism)oraz sekwencjonowania.Wyniki: Analiza polimorfizmu konformacji pojedynczych nici DNA w gradiencie temperatury wykazała zmianę ruchliwości elektroforetycznejw egzonie 8 genu AR. W wyniku sekwencjonowania egzonu 8 wykryto mutację punktową typu missens. Mutacja, dotychczasnie opisywana, ma charakter tranzycji c.T3816 > C i powoduje zmianę S901P w łańcuchu aminokwasowym (w oparciu o najnowsząsekwencję referencyjną NCBI, NM 000044.2).Wnioski: Stwierdzenie nowej mutacji, c.T3816 > C w genie AR jest kolejnym dowodem potwierdzającym związek mutacji AR z fenotypemzespołu niewrażliwości na androgeny. (Endokrynol Pol 2013; 64 (5): 398–402)Introduction: Androgen receptor (AR) gene mutations are the most frequent cause of 46,XY disorders of sex development (DSD), andare associated with a variety of phenotypes ranging from phenotypic women (Complete Androgen Insensitivity Syndrome or CAIS)to milder degrees of undervirilisation (Partial Androgen Insensitivity Syndrome or PAIS) or men with infertility only (Mild AndrogenInsensitivity Syndrome or MAIS).In this paper, we present the results of clinical, endocrine and molecular trials in a patient hospitalised because of primary amenorrhoeawith typical phenotype of CAIS.Material and methods: The main objective of this study was to determine the molecular cause of androgen insensitivity syndrome ina 46,XY female patient. Molecular analysis of the AR gene was conducted using MSSCP (Multitemperature Single Strand ConformationPolymorphism) and sequencing methods.Results: MSSCP analysis showed changes in electrophoretic mobility in exon 8 of the AR gene. Sequencing analysis revealed a missensemutation which has not been previously described. This is a c.T3816 > C transition mutation which causes a S901P substitution in theamino acid chain (based on the latest NCBI reference sequence NM 000044.2).Conclusions: The identified c.T3816 > C mutation in AR gene provides further evidence for the correlation between specific AR mutationsand phenotype corresponding to androgen insensitivity.(Endokrynol Pol 2013; 64 (5): 398–402

MicroRNAs Which Can Prognosticate Aggressiveness of Bladder Cancer

Bladder cancer (BC) is still characterized by a very high death rate in patients with this disease. One of the reasons for this is the lack of adequate markers which could help determine the biological potential of the tumor to develop into its invasive stage. It has been found that some microRNAs (miRNAs) correlate with disease progression. The purpose of this study was to identify which miRNAs can accurately predict the presence of BC and can differentiate low grade (LG) tumors from high grade (HG) tumors. The study included 55 patients with diagnosed bladder cancer and 30 persons belonging to the control group. The expression of seven selected miRNAs was estimated with the real-time PCR technique according to miR-103-5p (for the normalization of the results). Receiver operating characteristics (ROC) curves and the area under the curve (AUC) were used to evaluate the feasibility of using selected markers as biomarkers for detecting BC and discriminating non-muscle invasive BC (NMIBC) from muscle invasive BC (MIBC). For HG tumors, the relevant classifiers are miR-205-5p and miR-20a-5p, whereas miR-205-5p and miR-182-5p are for LG (AUC = 0.964 and AUC = 0.992, respectively). NMIBC patients with LG disease are characterized by significantly higher miR-130b-3p expression values compared to patients in HG tumors

Genetic Factors of Idiopathic Gigantomastia: Clinical Implications of Aromatase and Progesterone Receptor Polymorphisms

The role of estrogen, progesterone, their receptors and aromatase in the development of the breast is well documented. In this study we examined the association of genetic variants of progesterone receptor (PGR) and aromatase (CYP19A1) genes with gigantomastia risk. We conducted a case-control study among 124 women: 60 with gigantomastia and 64 controls. We examined the single nucleotide polymorphisms (SNPs) for CYP19A1 (rs749292 and rs7172156) and PGR (rs1042838). Our results showed that allele G in rs749292 (CYP19A1) increased the risk of gigantomastia, but not significantly (p = 0.09). There is a correlation between rs1042838 (PGR) and waist-to-hip ratio (WHR) in women with gigantomastia-AC genotype correlates with lower WHR and CC with higher WHR. There were no correlations between the onset of gigantomastia, the age of menarche and the length of the menstrual cycle, and rs1042838, rs749292 and rs7172156. We did not find differences in the SNP of PGR (rs1042838) between women with gigantomastia and controls. However, our findings showed more frequent G allele in CYP19A1 (rs749292) in women with gigantomastia