hrp0086fc7.6 | Gonads & DSD | ESPE2016

Whole-Exome Sequencing Reveals RAD51B Variant in Two Sisters with Primary Ovarian Failure

Franca Monica , Funari Mariana , Nishi Mirian , Domenice Sorahia , Latronico Ana Claudia , Jorge Alexander , Lerario Antonio , Mendonca Berenice

Background: Primary ovarian failure (POF) is a major cause of female infertility. POF is characterized by amenorrhea, hypo-estrogenism and elevated gonadotrophin levels. In POF disorder, several genetic alterations have been described, however in most of the patients the etiology of this disorder remains unknown.Objective and hypotheses: To identify new genes implicated in the development of POF using Next-Generation Sequencing (NGS).<p class="abstex...

hrp0086rfc6.2 | Syndromes: Mechanisms and Management | ESPE2016

RAB3IP and DGCR8 as a Potentially Pathogenic Novel Candidate Gene Involving in Growth Disorders

Homma Thais , Funari Mariana , Lerario Antonio , Freire Bruna , Nishi Mirian , Yamamoto Guilherme , Naslavsky Michel , Zatz Mayana , Arnhold Ivo , Jorge Alexander

Background: The majority of children with short stature are classified as idiopathic short stature. Whole exome sequencing can help identify genetic causes of short stature.Methods: We recruited 10 children with short stature of unknown etiology. We conducted whole exome sequencing of the patients and their family members. We used an analysis pipeline to identify rare nonsynonymous genetic variants that might cause the short stature. All rare allelic var...

hrp0086p1-p369 | Gonads &amp; DSD P1 | ESPE2016

Long-Term Follow-Up of Patients with 46,XY Partial Gonadal Dysgenesis Accordingly Gender Assignment

Gomes Nathalia , Costa Elaine , Zamboni Aline , Nishi Mirian , Batista Rafael , Cunha Flavia , Inacio Marlene , Domenice Sorahia , Mendonca Berenice

Background: Studies on the follow-up of 46,XY partial gonadal dysgenesis (PGD) patients till adulthood are scarce and it is important to provide information to parents on the prognosis of gonadal dysgenesis.Objective and hypotheses: To analyze the long term outcomes of 46XY PGD patients in both social sexes regarding testosterone production, social sex adaption and genotype.Method: Retrospective longitudinal study conducted at Hosp...

hrp0084lbp-1261 | Late Breaking Posters | ESPE2015

POLR3H Variant is Associated with Primary Ovarian Failure in Two Families

Franca Monica , Funari Mariana , Domenice Sorahia , Nishi Mirian , Costa Elaine , Gontijo Leticia , Latronico Ana Claudia , Jorge Alexander , Lerario Antonio , Mendonca Berenice

Background: Primary ovarian failure (POF) is a major cause of female infertility. POF is characterized by amenorrhea, hypo-estrogenism, and elevated gonadotrophin levels. In POF disorder, several genetic alterations have been described, however in most of the patients the etiology of this disorder remains unknown.Objective and hypotheses: To identify new genes implicated in the development of POF using whole-exome sequencing (WES)....

hrp0092p1-270 | Sex Differentiation, Gonads and Gynaecology or Sex Endocrinology (1) | ESPE2019

Large Spectrum of DSD Phenotype Caused by Pathogenic Variants in Wilms Tumor Suppressor Gene 1

Ferrari Maria Tereza Martins , Domenice Sorahia , Mendonça Berenice Bilharino , Moraes Daniela Rodrigues , Batista Rafael Loch , Gomes Nathalia Lisboa , Nishi Mirian Yumie , Sircili Maria Helena , Paula Tatiana Evelin , Costa Eduardo , Costa Elaine Maria Frade

Introduction: The Wilms tumor suppressor gene 1 (WT1) plays an essential role in urogenital and kidney development. Heterozygous germline mutations in WT1 have been classically associated with Denys–Drash (DDS) and Frasier syndrome (FS). Exonic missense mutations in the zinc-finger region are the cause of DDS and mutations affecting the canonic donor KTS splice site of intron 9 are the cause of FS. New phenotypes, as 46,XX testicular DSD...

hrp0092p3-219 | Sex Differentiation, Gonads and Gynaecology or Sex Endocrinology | ESPE2019

Final Adult Height in SRY-Negative 46,XX Ovotesticular Differences of Sex Development Individuals

Martins Ferrari Maria Tereza , Moraes Rodrigues Daniela , Lisboa Gomes Nathalia , Yumi Nishi Mirian , Loch Batista Rafael , Maria Frade Costa Elaine , Bilharinho Mendonca Berenice , Domenice Sorahia , Marques Cruz Patricia Sales , Sircili Maria Helena

Introduction: Differences of sex development (DSD) encompass a variety of conditions with atypical development of chromosomal, gonadal or anatomic sex. 46, XX ovotesticular (OT) DSD is a rare condition, in which the presence of testicular and ovarian tissues is identified in the same individual. These patients present variable phenotypes with a wide spectrum of atypical genitalia and their sex assignment can be male or female. Short stature is a frequent issue...

hrp0082p2-d2-574 | Sex Development (1) | ESPE2014

Analysis of Steroid 5-Alpha Reductase 2 (SRD5A2) Gene in Patients with 46,XY Disorder of Sex Development

de Souza Giselle Neres , Machado Aline Zamboni , Prado Arnhold Ivo Jorge , Mendonca Berenice , Palma Sircili Maria Helena , Nishi Mirian Yumie , Barbosa Silva Rosana , Frade Costa Elaine Maria , Domenice Sorahia

Background: The diagnosis of 46,XY disorder of sex development (DSD) due to 5-alpha reductase 2 (5α-RD2) deficiency has been based on testosterone:dihydrotestosterone (T:DHT) ratio, urinary steroid profiling and mutational analysis of SRD5A2 gene. The biochemical hallmarks of 5α-RD2 deficiency include increased T:DHT ratio. However, several difficulties are observed in the DHT measurement leading to misdiagnosis. The mutational analysis of the SRD5A2 has been propose...

hrp0084lbp-1268 | Late Breaking Posters | ESPE2015

Genetic Causes of Disproportional Short Stature Identified by Whole Exome Sequencing

Funari Mariana F A , Vasques Gabriela A , Lerario Antonio M , Freire Bruna L , Nishi Mirian Y , Franca Monica M , Shinjo Sueli M O , Marie Suely K N , Arnhold Ivo J P , Jorge Alexander A L

Background: Disproportional short stature (DSS) is the most frequent clinical presentation of skeletal dysplasias, which are a heterogeneous group of more than 450 disorders of bone. Skeletal survey is important to establish the diagnosis and to guide the genetic test, but has several limitations, especially in mild and atypical cases.Objective and hypotheses: To identify the genetic aetiology of DSS by exome sequencing.Method: Who...

hrp0092p1-135 | Sex Differentiation, Gonads and Gynaecology or Sex Endocrinology | ESPE2019

Combining Clinical and Genetic Approaches in Diagnosing a Large Brazilian Cohort of Patients with 46,XY Differences of Sex Development (DSD)

Gomes Nathalia Lisboa , Batista Rafael Loch , Nishi Mirian Y , Marcondes Antonio , Silva Tatiane E. , Funari Mariana , Faria Júnior José Antônio Diniz , Silva Daniela Moraes , Montenegro Luciana , Frade Costa Elaine Maria , Jorge Alexander Augusto , Domenice Sorahia , Mendonca Berenice Bilharinho

Background: Most published studies on 46,XY DSD focused on genetic findings without association with biochemical work-up.Objectives: To retrospectively analyze the clinical and genetic findings of a large cohort of 46,XY DSD patients.Methods: 285 non-syndromic 46,XY DSD individuals (192 sporadic and 89 familial cases) were studied. LH, FSH, testosterone (T), androstenedione (A) wer...

hrp0089fc8.5 | Sex differentiation, Gonads and Gynaecology or Sex Endocrinology | ESPE2018

DEAH-Box Helicase 37defects (DXH37) Deffects are a Novel Cause of 46,XY Gonadal Dysgenesis

Gomes Nathalia , Silva Thatiana , Lerario Antonio , Batista Rafael Loch , Junior Jose Antonio Faria , Moraes Daniela , Costa Elaine Maria Frade , Nishi Mirian , Carvalho Luciani Renata , Forclaz Maria Veronica , Papazian Regina , Martinez-Aguayo Alejandro , de Paula Leila Pedroso , Carvalho Filomena Marino , Vilain Erick , Barseghyan Hayk Barseghyan , Keegan Catherine , Domenice Sorahia , Mendonca Berenice Bilharinho

Background: 46,XY gonadal dysgenesis (GD) is a spectrum disorder which lead to variable degrees of atypical external genitalia, ranging from female to micropenis and absent of gonadal tissue (known as Embryonic Testicular Regression Syndrome -ETRS). Most patients with 46,XY GD remains without a molecular diagnosis.Objective: To report the DEAH-box helicase 37 gene (DHX37) as a novel candidate for the GD etiology.Patients a...