scholarly journals Modern opportunities and indications for genetic diagnosis of male infertility

2019 ◽  
pp. 3-15
Author(s):  
Т.М. Сорокина ◽  
О.А. Соловова ◽  
В.Б. Черных
Keyword(s):  
Male Infertility ◽  
Recurrent Miscarriage ◽  
Genetic Diagnosis ◽  
Disorders Of Sex Development ◽  
Gene Mutations ◽  
Genomic Analysis ◽  
Copy Number Variations ◽  
Genetic Causes ◽  
Sex Development ◽  
Genetic Examination

Тяжелые формы мужского и женского бесплодия, привычного невынашивания беременности, аномалий формирования пола часто обусловлены генетическими причинами или связаны с генетическими факторами. Медико-генетическое обследование и консультирование пациентов с нарушением репродукции зачастую ограничивается использованием стандартных рутинных исследований, поэтому не позволяет выявить многие наследственные формы репродуктивной патологии. Методы геномного анализа позволяют повысить эффективность диагностики генетически обусловленных нарушений репродукции, вызванных генными мутациями и вариациями числа копий (CNV), но их пока широко не используют в практическое медицине. В статье рассмотрены современные возможности медико-генетического обследования мужчин с нарушением фертильности, а также приведены показания и алгоритмы диагностики генетических причин мужского бесплодия, связанного с различными формами патозооспермии. Evere forms of male and female infertility, recurrent miscarriage, abnormalities in disorders of sex development are often due to genetic causes or are associated with genetic factors. Genetic examination and counseling of patients with reproductive problems is often limited to the use of standard routine techniques, therefore, it is not possible to identify many hereditary forms of reproductive pathology. Genomic analysis methods can improve the diagnosis of genetic reproductive disorders caused by gene mutations and copy number variations (CNVs), but they are not yet widely used in practical medicine. The article discusses the modern possibilities of medical-genetic examination of infertile men with, as well as the indications and diagnostic algorithms for the genetic causes of male infertility associated with various forms of pathozoospermia.

scholarly journals GENETICS IN ENDOCRINOLOGY: Approaches to molecular genetic diagnosis in the management of differences/disorders of sex development (DSD): position paper of EU COST Action BM 1303 ‘DSDnet’

2018 ◽  
Vol 179 (4) ◽  
pp. R197-R206 ◽  
Author(s):  
L Audí ◽  
S F Ahmed ◽  
N Krone ◽  
M Cools ◽  
K McElreavey ◽  
...  
Keyword(s):  
Candidate Genes ◽  
Best Practice ◽  
Molecular Genetic ◽  
Genetic Diagnosis ◽  
Disorders Of Sex Development ◽  
Initial Step ◽  
Copy Number Variations ◽  
Position Paper ◽  
Sex Development ◽  
Complementary Approach

The differential diagnosis of differences or disorders of sex development (DSD) belongs to the most complex fields in medicine. It requires a multidisciplinary team conducting a synoptic and complementary approach consisting of thorough clinical, hormonal and genetic workups. This position paper of EU COST (European Cooperation in Science and Technology) Action BM1303 ‘DSDnet’ was written by leading experts in the field and focuses on current best practice in genetic diagnosis in DSD patients. Ascertainment of the karyotpye defines one of the three major diagnostic DSD subclasses and is therefore the mandatory initial step. Subsequently, further analyses comprise molecular studies of monogenic DSD causes or analysis of copy number variations (CNV) or both. Panels of candidate genes provide rapid and reliable results. Whole exome and genome sequencing (WES and WGS) represent valuable methodological developments that are currently in the transition from basic science to clinical routine service in the field of DSD. However, in addition to covering known DSD candidate genes, WES and WGS help to identify novel genetic causes for DSD. Diagnostic interpretation must be performed with utmost caution and needs careful scientific validation in each DSD case.

WT1 Pathogenic Variants are Associated with a Broad Spectrum of Differences in Sex Development Phenotypes and Heterogeneous Progression of Renal Disease

2021 ◽  
pp. 1-9
Author(s):  
Maria T.M. Ferrari ◽  
Andreia Watanabe ◽  
Thatiane E. da Silva ◽  
Nathalia L. Gomes ◽  
Rafael L. Batista ◽  
...  
Keyword(s):  
Kidney Development ◽  
Wilms Tumor ◽  
Genetic Diagnosis ◽  
Germ Cell Tumors ◽  
Disorders Of Sex Development ◽  
Medical Attention ◽  
Primary Amenorrhea ◽  
Normal Female ◽  
Sex Development ◽  
Pathogenic Variants

Wilms’ tumor suppressor gene 1 (<i>WT1</i>) plays an essential role in urogenital and kidney development. Heterozygous germline pathogenic allelic variants of <i>WT1</i> have been classically associated with Denys–Drash syndrome (DDS) and Frasier syndrome (FS). Usually, exonic pathogenic missense variants in the zinc finger region are the cause of DDS, whereas pathogenic variants affecting the canonic donor lysine-threonine-serine splice site in intron 9 cause FS. Phenotypic overlap between <i>WT1</i> disorders has been frequently observed. New <i>WT1</i> variant-associated phenotypes, such as 46,XX testicular/ovarian-testicular disorders of sex development (DSD) and primary ovarian insufficiency, have been reported. In this report, we describe the phenotypes and genotypes of 7 Brazilian patients with pathogenic <i>WT1</i> variants. The molecular study involved Sanger sequencing and massively parallel targeted sequencing using a DSD-associated gene panel. Six patients (5 with a 46,XY karyotype and 1 with a 46,XX karyotype) were initially evaluated for atypical genitalia, and a 46,XY patient with normal female genitalia sought medical attention for primary amenorrhea. Germ cell tumors were identified in 2 patients, both with variants affecting alternative splicing of <i>WT1</i> between exons 9 and 10. Two pathogenic missense <i>WT1</i> variants were identified in two 46,XY individuals with Wilms’ tumors; both patients were &#x3c;1 year of age at the time of diagnosis. A novel <i>WT1</i> variant<i>,</i> c.1453_1456 (p.Arg485Glyfs*14), was identified in a 46,XX patient with testicular DSD. Nephrotic proteinuria was diagnosed in all patients, including 3 who underwent renal transplantation after progressing to end-stage kidney disease. The expanding phenotypic spectrum associated with <i>WT1</i> variants in XY and XX individuals confirms their pivotal role in gonadal and renal development as well as in tumorigenesis, emphasizing the clinical implications of these variants in genetic diagnosis.

Functional characterization of five NR5A1 gene mutations found in patients with 46,XY disorders of sex development

2017 ◽  
Vol 39 (1) ◽  
pp. 114-123 ◽  
Author(s):  
Helena Fabbri-Scallet ◽  
Maricilda Palandi de Mello ◽  
Gil Guerra-Júnior ◽  
Andréa Trevas Maciel-Guerra ◽  
Juliana Gabriel Ribeiro de Andrade ◽  
...  
Keyword(s):  
Functional Characterization ◽  
Disorders Of Sex Development ◽  
Gene Mutations ◽  
Sex Development

Investigation of androgen receptor gene mutations in a series of 21 patients with 46,XY disorders of sex development

2015 ◽  
Vol 28 (11-12) ◽  
Author(s):  
Vehap Topcu ◽  
Hatice Ilgin-Ruhi ◽  
Zeynep Siklar ◽  
Halil Gurhan Karabulut ◽  
Merih Berberoglu ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Sequence Analysis ◽  
Receptor Gene ◽  
Correct Diagnosis ◽  
Disorders Of Sex Development ◽  
Gene Mutations ◽  
Androgen Receptor Gene ◽  
Direct Sequence ◽  
Sex Development ◽  
Direct Sequence Analysis

AbstractAndrogen receptor (We direct sequenced all eight exons of theWe detectedDespite the fact that T/DHT ratio is frequently used in diagnosis of AIS, lack of precisely determined cutoffs compromises correct diagnosis. Hence, depending on clinical and biochemical findings solely may delay correct diagnosis. Direct sequence analysis of the

scholarly journals The laboratory in the multidisciplinary diagnosis of differences or disorders of sex development (DSD)

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Maria Luisa Granada ◽  
Laura Audí
Keyword(s):  
Differential Diagnosis ◽  
Candidate Genes ◽  
Steroid Hormones ◽  
Gene Dosage ◽  
Disorders Of Sex Development ◽  
Diagnostic Algorithm ◽  
Genetic Data ◽  
Gonadal Hormones ◽  
Copy Number Variations ◽  
Sex Development

Abstract Objectives 46,XY differences/disorders of sex development (DSD) involve an abnormal gonadal and/or genital (external and/or internal) development caused by lack or incomplete intrauterine virilization, with or without the presence of Müllerian ducts remnants. Content Useful biochemical markers for differential diagnosis of 46,XY DSD include hypothalamic-pituitary-gonadal hormones such as luteinizing and follicle-stimulating hormones (LH and FSH; in baseline or after LHRH stimulation conditions), the anti-Müllerian hormone (AMH), inhibin B, insulin-like 3 (INSL3), adrenal and gonadal steroid hormones (including cortisol, aldosterone, testosterone and their precursors, dihydrotestosterone and estradiol) and the pituitary ACTH hormone. Steroid hormones are measured at baseline or after stimulation with ACTH (adrenal hormones) and/or with HCG (gonadal hormones). Summary Different patterns of hormone profiles depend on the etiology and the severity of the underlying disorder and the age of the patient at diagnosis. Molecular diagnosis includes detection of gene dosage or copy number variations, analysis of candidate genes or high-throughput DNA sequencing of panels of candidate genes or the whole exome or genome. Outlook Differential diagnosis of 46,XX or 46,XY DSD requires a multidisciplinary approach, including patient history and clinical, morphological, imaging, biochemical and genetic data. We propose a diagnostic algorithm suitable for a newborn with DSD that focuses mainly on biochemical and genetic data.

Morphological analysis of testicles in cats with disorders of sex development

2017 ◽  
Vol 20 (1) ◽  
pp. 123-131 ◽  
Author(s):  
S. Dzimira ◽  
W. Nizanski ◽  
J.A. Madej
Keyword(s):  
Blood Vessels ◽  
Polyclonal Antibodies ◽  
S100 Protein ◽  
Smooth Muscles ◽  
Disorders Of Sex Development ◽  
Gene Mutations ◽  
Control Group ◽  
Histological Structure ◽  
Sex Development ◽  
Hematoxylin And Eosin

Abstract Disorders of sex development (DSD) are rare in cats. They can be caused by chromosomal aberrations, gene mutations or other undefined factors. The aim of the present study was to compare the histological structure and immunohistochemical reactivity of testes in cats with DSD and in healthy cats. The research material consisted of the gonads of four cats - phenotypic males with an incorrect structure of the reproductive system. The control group consisted of the testes of four healthy cats - routinely castrated phenotypical males. The material was fixed with formalin and embedded in paraffin; the sections were stained with hematoxylin and eosin. The immunohistochemical investigation were performed using monoclonal and polyclonal antibodies directed against desmin, vimentin, actin of smooth muscles, S100 protein and MCM3 protein. The results obtained allow concluding that the testes of cats with DSD differed in certain respects, mainly in the number of blood vessels, from the normal testes. Moreover, the results of immunohistochemical examination indicate that in the testes of cats with DSD the number of supporting cells is lower, the amount of interstitial cells is comparable and spermatogenesis is correct es compared to those determined in the control gonads. The number of blood vessels in cats with DSD is reduced by about 30%. It confirms the recommendations for castration of these animals in order to eliminate the potential inheritance of sex development disorders.

scholarly journals Disorders of sex development: advances in genetic diagnosis and challenges in management

2015 ◽  
pp. 165 ◽  
Author(s):  
Faisal Ahmed ◽  
Andreas Kyriakou ◽  
Edward Tobias ◽  
Angela Lucas-Herald ◽  
Ruth McGowan
Keyword(s):  
Genetic Diagnosis ◽  
Disorders Of Sex Development ◽  
Sex Development

scholarly journals Integrated small copy number variations and epigenome maps of disorders of sex development

2016 ◽  
Vol 3 (1) ◽  
Author(s):  
Ina E Amarillo ◽  
Isabelle Nievera ◽  
Andrew Hagan ◽  
Vishwa Huchthagowder ◽  
Jennifer Heeley ◽  
...  
Keyword(s):  
Copy Number ◽  
Disorders Of Sex Development ◽  
Copy Number Variations ◽  
Sex Development

scholarly journals Cis-Regulatory Control of Mammalian Sex Determination

2021 ◽  
pp. 1-18
Author(s):  
Meshi Ridnik ◽  
Stefan Schoenfelder ◽  
Nitzan Gonen
Keyword(s):  
Sex Determination ◽  
Cell Fate ◽  
Developmental Disorders ◽  
Genetic Diagnosis ◽  
Disorders Of Sex Development ◽  
Regulatory Elements ◽  
Regulatory Control ◽  
Male Factor ◽  
Cis Acting ◽  
Sex Development

Sex determination is the process by which an initial bipotential gonad adopts either a testicular or ovarian cell fate. The inability to properly complete this process leads to a group of developmental disorders classified as disorders of sex development (DSD). To date, dozens of genes were shown to play roles in mammalian sex determination, and mutations in these genes can cause DSD in humans or gonadal sex reversal/dysfunction in mice. However, exome sequencing currently provides genetic diagnosis for only less than half of DSD patients. This points towards a major role for the non-coding genome during sex determination. In this review, we highlight recent advances in our understanding of non-coding, cis-acting gene regulatory elements and discuss how they may control transcriptional programmes that underpin sex determination in the context of the 3-dimensional folding of chromatin. As a paradigm, we focus on the <i>Sox9</i> gene, a prominent pro-male factor and one of the most extensively studied genes in gonadal cell fate determination.

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