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

scholarly journals Functional characterization of novel NR5A1  variants reveals multiple complex roles in disorders of sex development

2017 ◽  
Vol 39 (1) ◽  
pp. 124-139 ◽  
Author(s):  
Gorjana Robevska ◽  
Jocelyn A. van den Bergen ◽  
Thomas Ohnesorg ◽  
Stefanie Eggers ◽  
Chloe Hanna ◽  
...  
Keyword(s):  
Functional Characterization ◽  
Disorders Of Sex Development ◽  
Sex Development

scholarly journals Functional characterization of naturally occurring NR3C2 gene mutations in Italian patients suffering from pseudohypoaldosteronism type 1

2007 ◽  
Vol 156 (2) ◽  
pp. 249-256 ◽  
Author(s):  
Antonio Balsamo ◽  
Alessandro Cicognani ◽  
Monia Gennari ◽  
Wolfgang G Sippell ◽  
Soara Menabò ◽  
...  
Keyword(s):  
Receptor Gene ◽  
Functional Characterization ◽  
Clinical Signs ◽  
Gene Mutations ◽  
Ethnic Origin ◽  
Snp Markers ◽  
Italian Population ◽  
Pseudohypoaldosteronism Type

Objective: The renal form of pseudohypoaldosteronism type 1 (PHA1) is a rare disease caused by mutations in the human mineralocorticoid receptor gene (NR3C2). Design: Aim of the study was to analyze the NR3C2 gene in three Italian patients with clinical signs of renal PHA1 and to evaluate the distribution of the -2G > C, c.538A > G, and c.722C > T single nucleotide polymorphism (SNP) pattern in the PHA1 patients and in 90 controls of the same ethnic origin. Methods: Analysis of the NR3C2 gene sequence and of the polymorphic SNP markers. Functional characterization of the detected novel NR3C2 mutations utilizing aldosterone-binding assays and reporter gene transactivation assays. Results: One novel nonsense (Y134X) and one novel frameshift (2125delA) mutation were detected. They exhibited no aldosterone binding and no transactivation abilities. No mutation was detected in the third patient. Haploinsufficiency of NR3C2 was ruled out by microsatellite analysis in this patient. The c.722T SNP was detected in 97% of alleles in the Italian population which is significantly different from the general German or US population. Conclusions: Molecular analysis of the NR3C2 gene in PHA1 patients is warranted to detect novel mutations in order to clarify the underlying genetic cause, which may extend the insight into relevant functional regions of the hMR protein. The effect the different distribution of the c.722T SNP is not clear to date. Further studies are necessary to provide evidence as to a possible advantage of a less sensitive hMR in southern countries.

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

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 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 Disorders of sex development: Genetic characterization of a patient cohort

2019 ◽  
Author(s):  
Mary Garc�a-Acero ◽  
Olga Moreno-Ni�o ◽  
Fernando Su�rez-Obando ◽  
M�nica Molina ◽  
Mar�a Manotas ◽  
...  
Keyword(s):  
Genetic Characterization ◽  
Disorders Of Sex Development ◽  
Patient Cohort ◽  
Sex Development

Functional characterization of natural telomerase mutations found in patients with hematologic disorders

Blood ◽  
2006 ◽  
Vol 109 (2) ◽  
pp. 524-532 ◽  
Author(s):  
Zhong-Tao Xin ◽  
Adam D. Beauchamp ◽  
Rodrigo T. Calado ◽  
Jennifer W. Bradford ◽  
Joshua A. Regal ◽  
...  
Keyword(s):  
Bone Marrow Failure ◽  
Functional Characterization ◽  
Gene Mutations ◽  
Dyskeratosis Congenita ◽  
Dominant Negative ◽  
Sequence Variants ◽  
Hematologic Disorders ◽  
Bone Marrow Failure Syndromes ◽  
Human Telomerase

Abstract Human telomerase hTERC RNA serves as a template for the catalytic hTERT protein to synthesize telomere repeats at chromosome ends. We have recently shown that some patients with bone marrow failure syndromes are heterozygous carriers for hTERC or hTERT mutations. These sequence variations usually lead to a compromised telomerase function by haploinsufficiency. Here, we provide functional characterization of an additional 8 distinct hTERT sequence variants and 5 hTERC variants that have recently been identified in patients with dyskeratosis congenita (DC) or aplastic anemia (AA). Among the mutations, 2 are novel telomerase variants that were identified in our cohort of patients. Whereas most of the sequence variants modulate telomerase function by haploinsufficiency, 2 hTERC variants with sequence changes located within the template region appear to act in a dominant-negative fashion. Inherited telomerase gene mutations, therefore, operate by various mechanisms to shorten telomere lengths, leading to limited marrow stem cell reserve and renewal capacity in patients with hematologic disorders.

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