hrp0086fc6.5 | Syndromes: Mechanisms and Management | ESPE2016

Pathogenic Copy Number Variants are Frequently Identified in Children with Short Stature of Unknown Etiology

Canton Ana , Homma Thais , Furuya Tatiane , Roela Rosimeire , Arnhold Ivo , Jorge Alexander

Background: The etiology of short stature is heterogeneous, often encompassing complex genetic disorders of difficult diagnosis. Analysis of chromosomic copy number variants (CNVs) has been demonstrating the important role of these genomic imbalances in population diversity and human disease.Objective and hypotheses: To analyze the frequency and describe novel submicroscopic chromosomal CNVs in a group of patients with short stature of unknown cause....

hrp0086rfc6.6 | Syndromes: Mechanisms and Management | ESPE2016

Growth Hormone (GH) Deficiency Type II: Clinical and Molecular Evidence of Impaired Regulated GH Secretion Due to an Gln181Arg GH-1 Gene Mutation

Miletta Maria Consolata , Eble Andree , Arnhold Ivo J P , Dauber Andrew , Fluck Christa , Pandey Amit

Background: Main features of the autosomal dominant form of GH deficiency (IGHD II) include markedly reduced secretion of GH combined with low concentrations of IGF-I leading to short stature.Objective and hypotheses: We report on a girl referred for assessment of short stature (−4.6 SDS) at a chronological age of 7 yr 10 mo. The GH deficiency was confirmed by standard GH provocation tests, which revealed severely reduced GH and IGF-I concentration...

hrp0084p3-1034 | Growth | ESPE2015

Birth Characteristics Influence the Male to Female Diagnostic Prevalence of Idiopathic GH Deficiency

Camacho-Hubner Cecilia , Lindberg Anders , Arnhold Ivo J P , Ranke Michael B

Background: A greater number of male (M) vs female (F) patients are diagnosed with GH deficiency (GHD). M have larger birth weight (BW), length and head circumference (HC) compared to F; these characteristics could contribute to subtle cephalo-pelvic disproportion and mild head trauma possibly contributing to idiopathic GHD (IGHD) and multiple pituitary hormone deficiencies (MPHD).Objective: To determine birth characteristics including mode of delivery a...

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...

hrp0089p1-p177 | Growth & Syndromes P1 | ESPE2018

Genetic Investigation of Children with Syndromic Prenatal Onset Short Stature

Homma Thais , Freire Bruna , Ronjo Rachel , Dauber Andrew , Funari Mariana , Lerario Antonio , Arnhold Ivo , Canton Ana , Sugayama Sofia , Bertola Debora , Kim Chong , Malaquias Alexsandra , Jorge Alexander

Background: Patients born small for gestational age (SGA) with additional syndromic features to short stature are likely to present with genetic causes.Aim: To perform a clinical and genetic-molecular investigation of a group of syndromic SGA patients without catch-up growth.Methods: We selected 118 patients born SGA [birth weight and/or length standard deviation score (SDS) ≤−2 for gestational age] without catch-up gro...

hrp0082p1-d1-136 | Growth | ESPE2014

A Homozygous Point Mutation in the GH1 Promoter (−161T>C) Leads to Reduced GH Expression in Siblings with Isolated GH Deficiency

Madeira Joao , Martin Regina , Montenegro Luciana , Franca Marcela , Costalonga Everlayny , Correa Fernanda , Otto Aline , Arnhold Ivo , Freitas Helayne , Machado Ubiratan , Mendonca Berenice , Jorge Alexander , Carvalho Luciani

Introduction: Mutations in the GH1 promoter are a rare cause of isolated GH deficiency (IGHD). In order to find the molecular cause of short stature due to IGHD, three siblings (2 M) born to consanguineous parents without mutations in the GHRHR and GH1 coding regions were screened for mutations in the GH1 promoter and locus control region. All patients harbored two variants (c.−123T>C and −161C>T) in homozygous state in the GH1 promoter, not found in 100 co...

hrp0082p1-d3-100 | Sex Development | ESPE2014

Quality of Life in a Large Cohort of Adult Brazilian Patients with 46,XX and 46,XY Disorders of Sex Development from a Single Tertiary Centre

Amaral Rita , Inacio Marlene , Brito Vinicius , Bachega Tania , Oliveira Ari , Domenice Sorahia , Denes Francisco , Sircilli Maria Helena , Arnhold Ivo , Madureira Guiomar , Gomes Larissa , Costa Elaine , Mendonca Berenice

Background: Few studies have focused on the quality of life (QoL) of patients with disorders of sex development (DSD).Objective and hypotheses: Our aim was to evaluate QoL in DSD patients with defined diagnoses followed until adulthood in a single tertiary centre.Method: Subjects: adult DSD patients (56 patients with 46,XX DSD – 49 with female social sex and seven with male social sex as well as 88 patients with 46,XY DSD &#15...

hrp0084fc6.5 | Gonads & DSD | ESPE2015

Characterisation of Mutations in the Androgen Receptor Identified in 38 Brazilian Families with Complete or Partial Androgen Insensitivity Syndrome

Batista Rafael Loch , Santi Andreza , Arnhold Ivo J P , Cunha Flavia S , Costa Elaine M F , Mendonca Berenince B , Domenice Sorahia

Background: Androgen insensitivity syndrome (AIS) is a genetic disease X-linked, caused by functional abnormalities of the androgen receptor (AR). Mutations in the AR are associated with broad phenotypic spectrum from partial insensibility (PAIS) to complete insensitivity (CAIS).Objective and hypotheses: To characterize the mutations (MUT) identified in the AR in 38 Brazilian families with AIS. The MUT were analyzed considering their type, location in th...

hrp0084p2-535 | Puberty | ESPE2015

GH Deficiency with Advanced Bone Age: GHRH Receptor Mutation Detected by Exome Sequencing Associated to Non-Classical Congenital Adrenal Hyperplasia (CAH)

Correa Fernanda de Azevedo , Franca Marcela M , Fang Qing , Ma Qianyi , Bachega Tania A , Mendonca Berenice B , LJorge Alexander , Carvalho Luciani R , Camper Sally A , Arnhold Ivo J P

Background: Isolated Growth Hormone Deficiency (IGHD) is usually associated with a delayed bone age. A genetic cause for IGHD is more frequently found in patients with familial cases and/or consanguineous parents.Objective and hypotheses: To diagnose the genetic cause of IGHD and clarify the unusual clinical presentation of advanced bone age in one patient born to consanguineous parents.Method: Sanger sequencing of GH1, <e...

hrp0089fc9.1 | Pituitary, neuroendocrinology and Puberty 1 | ESPE2018

Novel Variants in the POU1F1 Beta Isoform are Associated with Isolated Growth Hormone Deficiency and Combined Pituitary Hormone Deficiency

Hoppmann Julia , Rockstroh-Lippold Denise , Gergics Peter , Nakaguma Marilena , Carvalho Luciani Renata Silveira , Pfaeffle Heike , Jamra Rami Abou , Jorge Alexander , Guo Michael H. , Dauber Andrew , Keller Eberhard , Camper Sally A. , Arnhold Ivo JP , Pfaeffle Roland

Background: Hypopituitarism is characterized by deficiency of one or more anterior pituitary hormones. POU1F1 mutations are the second most frequent known cause of combined pituitary hormone deficiency (CPHD). Patients are typically deficient in GH, TSH, and prolactin, although two unrelated cases were reported with isolated GH deficiency (IGHD). To date, all POU1F1 mutations have been reported for the predominantly expressed alpha isoform, which is a transcr...