Novel mutations segregating with Complete Androgen Insensitivity Syndrome and their molecular characteristics.
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE125222 | GEO | 2019/02/18
REPOSITORIES: GEO
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Project description:Novel mutations segregating with Complete Androgen Insensitivity Syndrome and their molecular characteristics.
| PRJNA515839 | ENA
Project description:We analyzed three cases of Complete Androgen Insensitivity Syndrome (CAIS) and report three hitherto undisclosed causes of the disease. RNA-Seq, Real-timePCR, Western immunoblotting, and immunohistochemistry were performed with the aim of characterizing the disease-causing variants. In case No.1, we have identified a novel androgen receptor (AR) mutation (c.840delT) within the first exon in the N-terminal transactivation domain. This thymine deletion resulted in a frameshift and thus introduced a premature stop codon at amino acid 282. In case No.2, we observed a nonsynonymous mutation in the ligand-binding domain (c.2491C>T). Case No.3 did not reveal AR mutation; however, we have found a heterozygous mutation in CYP11A1 gene, which has a role in steroid hormone biosynthesis. Comparative RNA-Seq analysis of CAIS and control revealed 4293 significantly deregulated genes. In patients with CAIS, we observed a significant increase in the expression levels of PLCXD3, TM4SF18, CFI, GPX8, and SFRP4, and a significant decrease in the expression of SPATA16, TSACC, TCP10L, and DPY19L2 genes (more than 10-fold, p < 0.05). Our findings will be helpful in molecular diagnostics of patients with CAIS, as well as the identified genes could be also potential biomarkers for the germ cells differentiation process.
| S-EPMC6861889 | biostudies-literature
Project description:This gene set contains skin fibroblasts from either labia majora of 46,XY sex reversed females having complete androgen insensitivity syndrome due to inactivation mutations of the androgen receptor gene and from the scrotum of normal males. Both, labia majora and scrotum origin from the same embryological anlagen, the labioscrotal swellings. The phenotypic difference is due to androgen dependent virilization in males. This is not possible in 46,XY patients with complete androgen insensitivity syndrome because the androgen receptor pathway is knocked out. A cell type comparison design experiment design type compares cells of different type for example different cell lines. Cell Line: genital skin fibroblasts from different locations mutant line: normal 46,XY male and 46,XY sex reversed female due to inactivating mutations of the androgen receptor gene Computed
2010-06-25 | E-GEOD-6797 | biostudies-arrayexpress
Project description:This gene set contains skin fibroblasts from either labia majora of 46,XY sex reversed females having complete androgen insensitivity syndrome due to inactivation mutations of the androgen receptor gene and from the scrotum of normal males. Both, labia majora and scrotum origin from the same embryological anlagen, the labioscrotal swellings. The phenotypic difference is due to androgen dependent virilization in males. This is not possible in 46,XY patients with complete androgen insensitivity syndrome because the androgen receptor pathway is knocked out. A cell type comparison design experiment design type compares cells of different type for example different cell lines. Cell Line: genital skin fibroblasts from different locations mutant line: normal 46,XY male and 46,XY sex reversed female due to inactivating mutations of the androgen receptor gene Keywords: cell_type_comparison_design
2007-10-20 | GSE6797 | GEO
Project description:Testicular cancer is the most common solid malignancy in young men. Given the many histological classifications of testicular tumours, seminoma is one of the most treatable cancers. The survival rate in early-stage disease was more than 90%. Thus, seminoma at the cellular and molecular levels, especially at the single-cell level, is worth studying. We performed a single-cell RNA sequencing (scRNA-seq) study on a patient who was diagnosed with testicular seminoma with lymph node metastasis. This study presented tumour tissue, PBMC, pelvic and renal hilus lymph node in a total of 18,206 high-quality single-cell transcriptome information. The characteristics of metastatic cell lineage were revealed by the comparison between different tumour cell subtypes at the scRNA level. A single-cell map of testicular seminoma with lymph node metastasis was constructed by scRNA-seq. We discovered the gene expression characteristics of the tumour cells in testicular seminoma, especially metastatic tumour cells. KRT8 and KRT18 were commonly expressed in the three tumour cell subtypes. However, TCF7L1, SCG3 and SV2C were the specifically expressed genes of tumour cell subtypes in primary tumour sites. Some molecular markers specifically expressed by the metastatic cell lineage, such as POU5F1, were identified. We revealed the molecular characteristics of testicular seminoma at the single-cell level, especially the metastatic tumour cells. This study could provide new insights into the diagnosis and treatment of testicular seminoma.
2022-03-25 | GSE197778 | GEO
Project description:The present study was carried out on a proband affected by Partial Androgen Insensitivity Syndrome (PAIS) and his family. The patient developed the primary RSC at 27 years. Three years after primary surgery, the patient developed a second primary (metachronous) rectal cancer relapsed one year later. The PAIS was also diagnosed in his cousin. Both cousins were found positive for the same missense androgen receptor (AR) gene mutation that was inherited from their asymptomatic mothers. The aim of this study was to identify constitutional genetic events that could have played a role in early onset of RSC in the proband. SNP-array analyses were carried out to investigate Copy Number Variations and Uniparental Disomy events as possible genetic causes linked to Colorectal Cancer pathogenesis.
2016-06-05 | GSE69613 | GEO
Project description:Complete androgen insensitivity syndrome (CAIS) is due to complete resistance to the action of androgens, determining a female phenotype in persons with a 46,XY karyotype and functioning testes. CAIS is caused by inactivating mutations in the androgen receptor gene (AR). It is organized in eight exons located on the X chromosome. Hundreds of genetic variants in the AR gene have been reported in CAIS. They are distributed throughout the gene with a preponderance located in the ligand-binding domain. CAIS mainly presents as primary amenorrhea in an adolescent female or as a bilateral inguinal/labial hernia containing testes in prepubertal children. Some issues regarding the management of females with CAIS remain poorly standardized (such as the follow-up of intact testes, the timing of gonadal removal and optimal hormone replacement therapy). Basic research will lead to the consideration of new issues to improve long-term well-being (such as bone health, immune and metabolic aspects and cardiovascular risk). An expert multidisciplinary approach is mandatory to increase the long-term quality of life of women with CAIS.
| S-EPMC7865707 | biostudies-literature
Project description:In this study, we used microarray analysis to investigate molecular differences underlying the determination of pigmentation in various skin types, and we used immunohistochemistry to validate the expression patterns of several interesting targets that were identified. Whole skin gene expression profile were investigated in three ethnic groups:1) Caucasian 2)Asian 3)African. In each group, 4 mm whole skin punch biopsies were taken from forearm of 10 subjects, and gene expression level were tested by agilent whole human genome microarray. Samples with mRNA degraded: African_skin_03, Asian_skin_02, Asian_skin_06, and Caucasian_skin_7.
2014-07-31 | E-GEOD-54638 | biostudies-arrayexpress
Project description:Transposable elements (TEs) comprise a large proportion of the eukaryote genomes. Yet it remains poorly understood how TEs influence the fitness of the hosts carrying them. Here, we empirically test the impact of TEs on the host fitness in the fission yeast Schizosaccharomyces pombe. We find that two families of TEs (Tf1 and Tf2 elements), both of which belong to long terminal repeat retrotransposons, are highly polymorphic among individual S. pombe strains. Only 13 complete Tf2 elements are identified in S. pombe laboratory strain 972. These 13 Tf2 elements integrated into host genomes in very recent time and are segregating within the S. pombe population. Through knocking out each of the 13 Tf2 elements in S. pombe strain 972, we find Tf2 knockout does not affect the host fitness, and Tf2 elements do not alter the expression of nearby genes. Challenged by diverse forms of stress, the Tf2 knockout strains do not exhibit different growth rates from wild-type strain. Together, we conclude that segregating complete Tf2 elements insertions are largely neutral to host fitness in the fission yeast. Our study provides genome-wide empirical support for the selfish nature of TEs in fission yeast.
| S-EPMC8634392 | biostudies-literature
Project description:IntroductionTo address the lack of medical education on lesbian, gay, bisexual, transgender, queer (LGBTQ), and difference in sex development-affected (DSD-affected) individuals, the University of Louisville initiated the eQuality project. The mission of eQuality is to promote mastery of the skills, knowledge, and attitudes required for excellent care for patients within the LGBTQ, gender-nonconforming, and DSD community. This problem-based learning (PBL) case was implemented to address both medical and psychosocial factors that affect individuals born with DSD and their families.MethodsStudents complete a 10-question multiple-choice pretest prior to distribution of the PBL case and a 10-question multiple-choice posttest after completion of the PBL. They also evaluate the efficacy of the case by answering three open-ended questions regarding comprehension, competence, and attitudes, as well as any barriers to acquisition and implementation of knowledge. Along with a specific lecture and patient panel, this piece helps to incorporate more information specifically on DSD into the curriculum.ResultsThe posttest average score was 20% higher than the pretest. The posttest (n = 144) had a range of 90% to 99% of students answering each question correctly, whereas the range for the pretest (n = 155) was from 29% to 94%.DiscussionBased on the objective assessment and student comments, learning increased through this PBL process. Despite this clear increase in knowledge, some students believed that either societal barriers or personal barriers would prevent them from implementing their newly gained knowledge in practice.
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