A5065177066- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Sexual Differentiation and Disorders
- Sperm and Testicular Function
- RNA Research and Splicing
- RNA modifications and cancer
- Renal and related cancers
- Animal Genetics and Reproduction
- Chromosomal and Genetic Variations
- RNA and protein synthesis mechanisms
- RNA Interference and Gene Delivery
- Cancer-related molecular mechanisms research
- Hormonal and reproductive studies
- Hormonal Regulation and Hypertension
- Genomics and Chromatin Dynamics
- Prenatal Screening and Diagnostics
- CRISPR and Genetic Engineering
- FOXO transcription factor regulation
- Circular RNAs in diseases
- Epigenetics and DNA Methylation
- Reproductive Biology and Fertility
- LGBTQ Health, Identity, and Policy
- Urological Disorders and Treatments
- Extracellular vesicles in disease
Polish Academy of Sciences
2011-2023
Institute of Human Genetics
2003-2023
Polish Academy of Learning
2020
Children's Memorial Health Institute
1999
<h3>Background</h3> The <i>Nanos</i> gene is a key translational regulator of specific mRNAs involved in <i>Drosophila</i> germ cell development. Disruption mammalian homologues, <i>Nanos2</i> or <i>Nanos3</i>, causes male infertility mice. In humans, however, no evidence <i>NANOS2</i> <i>NANOS3</i> mutations causing has been reported. Although <i>Nanos1</i> seems dispensable for mouse reproduction, we sought to analyse the first time its homologue infertile men. <h3>Methods</h3> A group 195...
46,XX subjects carrying the testis determining SRY gene usually have a completely male phenotype. In this study, five very rare cases of (two XX males and three true hermaphrodites) with various degrees incomplete masculinisation were analysed in order to elucidate cause sexual ambiguity despite presence gene. PCR amplification 20 Y chromosome specific sequences showed Yp fragment be much longer than hermaphrodites. FISH analysis combined RBG banding metaphase chromosomes four patients that...
The highly conserved Nanos gene was found to encode a translational repressor necessary for germ-cell development in lower organisms. mammalian homologue, Nanos2, recently be expressed the mouse germ cells. Since its disruption caused infertility exclusively males, we sought study significance of this human male reproduction. Here, describe first time expression pattern NANOS2 tissues and show that it is testis specific. We protein present prenatal cells at later stages spermatogenesis. To...
The 46,XX testicular DSD (disorder/difference of sexual development) and ovotesticular (46,XX TDSD OTDSD) phenotypes are caused by genetic rearrangements or point mutations resulting in imbalance between components the two antagonistic, pro-testicular pro-ovarian pathways; however, causes TDSD/OTDSD not fully understood, molecular diagnosis for many patients with conditions is unavailable. Only recently few WT1 (WT1 transcription factor; 11p13) gene were described a group OTDSD individuals....
Nanos RNA-binding proteins are critical factors of germline development throughout the animal kingdom and their dysfunction causes infertility. During evolution, mammalian paralogues adopted divergent roles in germ cell biology. However, molecular basis behind this divergence, such as target mRNAs, remains poorly understood. Our RNA-sequencing analysis a human primordial model-TCam-2 line revealed distinct pools genes involved cycle process downregulated upon NANOS1 NANOS3 overexpression. We...
Disorders/differences of sex development (DSD) cause profound psychological and reproductive consequences for the affected individuals, however, most are still unexplained at molecular level. Here, we present a novel gene, 3-hydroxy-3-methylglutaryl coenzyme A synthase 2 (HMGCS2), encoding metabolic enzyme in liver important energy production from fatty acids, that shows an unusual expression pattern developing fetal mouse gonads. Shortly after gonadal determination it is up-regulated testes...
We report the case of a female patient suffering from 46,XY disorder sexual development (DSD) with complete gonadal dysgenesis and Wiedemann-Steiner Syndrome (WDSTS). The coexistence these 2 conditions has not yet been reported. Using whole exome sequencing comparative genome hybridization array, we identified de novo <i>MLL/KMT2A</i> gene nonsense mutation which explains WDSTS phenotype. In addition, discovered novel genetic variants, could explain testicular observed in...
Identification of novel genes involved in sexual development is crucial for understanding disorders sex (DSD). Here, we propose a member the START domain family, X chromosome<i> STARD8,</i> as DSD candidate gene. We have identified missense mutation this gene 2 sisters with 46,XY gonadal dysgenesis, inherited from their heterozygous mother. Gonadal tissue one contained Leydig cells overloaded cholesterol droplets, i.e., structures previously patients carrying mutations...
In recent years, growing evidence demonstrates that mammalian Nanos RNA-binding proteins (Nanos1, Nanos2, and Nanos3), known for their indispensable roles in germline development, are overexpressed a variety of cancers. This overexpression contributes to various oncogenic properties including cancer growth, invasiveness, metastasis. Here, we highlight findings regarding the role mechanisms cancer. addition, present expression profiles human NANOS genes transcriptional regulators obtained...
Androgen insensitivity syndrome (AIS), manifesting incomplete virilization in 46,XY individuals, is caused mostly by androgen receptor (AR) gene mutations. Therefore, a search for AR mutations routine approach AIS diagnosis. However, some patients lack mutations, which complicates the Here, we describe patient suffering from partial (PAIS) and lacking The whole exome sequencing of his family members identified heterozygous FKBP4 mutation, c.956T>C (p.Leu319Pro), inherited mother. encodes...
Abstract The highly conserved Pumilio protein plays crucial roles in fertility of many organisms acting as a repressor translation, and causing infertility when mutated. Although one two human homologs, PUMILIO2 is expressed mainly the germ line, its role mammalian cell development has not been reported yet. To shed light on male we screened this gene for mutations 137 patients presenting variety phenotypes with spermatogenic failure. first variant, identified was single base substitution...
Mammalian Pumilio (PUM) proteins are sequence-specific, RNA-binding (RBPs) with wide-ranging roles. They involved in germ cell development, which has functional implications development and fertility. Although human PUM1 PUM2 closely related to each other recognize the same RNA binding motif, there is some evidence for diversity. To address that problem, first we used RIP-Seq RNA-Seq approaches, identified mRNA pools regulated by TCam-2 line, a male model. Second, applying global mass...
While two mouse NANOS paralogues, NANOS2 and NANOS3, are crucial for maintenance of germ cells by suppression apoptosis, the NANOS1 paralogue does not seem to regulate these processes. Previously, we described a human p.[(Pro34Thr);(Ser83del)] mutation associated with absence in seminiferous tubules infertile patients, which might suggest an anti-apoptotic role NANOS1. In this study, aimed determine potential influence on TCam-2 model investigating proliferation, cell cycle, apoptosis....
Regulation of proliferation, apoptosis and cell cycle is crucial for the physiology germ cells. Their malfunction contributes to infertility tumours. The kinesin KIF18A an important regulator those processes in animal Post-transcriptional regulation has not been extensively explored. Owing presence PUM-binding elements (PBEs), mRNA a potential target PUM proteins, where refers Pumilio RNA-binding proteins that act post-transcriptional gene regulation. We conducted RNA co-immunoprecipitation...
ABSTRACT Mammalian Pumilio (PUM) proteins are sequence-specific, RNA-binding with wide-ranging roles, including germ cell development that has functional implications in fertility. Although human PUM1 and PUM2 closely related to each other recognize the same RNA binding motif, there is some evidence for diversity, particularly their roles Here, by sequencing (RNA-Seq) approaches, we identified separate mRNA pools regulated male cells. Using global mass spectrometry-based profiling, distinct...
<b><i>Introduction:</i></b> 46,XY gonadal dysgenesis is a condition that characterised by undeveloped testes in individuals with male karyotype. Mutations many genes underlie this have been identified; however, there are still considerable number of patients an unknown genetic background. Recently, mutation the <i>STARD8</i> X-linked gene two sisters has reported. It was localised within START domain, whose homologue <i>Drosophila</i>...
ABSTRACT Regulation of proliferation, apoptosis and cell cycle is crucial for the physiology germ cells. Their malfunction contributes to infertility tumours. Kinesin KIF18A an important specific regulator which downregulates while promoting proliferation in animal models. Whereas regulation expression was studied at transcriptional level, its posttranscriptional has not been extensively explored. Due presence two PUM Binding Elements (PBEs) within 3’UTR, mRNA a potential target PUMs, well...