hrp0095p1-439 | Diabetes and Insulin | ESPE2022

Deciphering Monogenic Diabetes Mellitus in Spanish Pediatric Patients: A Cross-Sectional Study

Gomes Porras Mariana , Coral Barreda Bonis Ana , Salamanca Fresno Luis , González Casado Isabel , Campos Barros Ángel

Background and aims: The introduction of next-generation sequencing (NGS) as an essential tool for the routine molecular diagnosis of DM has highlighted the under-diagnosis of monogenic diabetes mellitus (MonDM). Accurate molecular diagnosis of the MonDM subtype has important implications for prognosis and choice of treatment, family counseling and health management, enabling precision medicine. The main objective was to clinically and molecularly characterize...

hrp0082p2-d2-470 | Growth (1) | ESPE2014

Severe Short Stature due to a Heterozygous igf1r Mutation With a Good Response to rhgh Therapy: a Family Study

Borras-Perez Victoria , Fernandez-Cancio Monica , Gomez-Nunez Ana , Catala-Puigbo M , Audi Laura , Campos-Barros Angel

Background: IGF1 resistance syndrome (IGF1RS) is characterized by intrauterine and postnatal growth deficit with normal or supranormal IGF1 levels. Additional features may include intellectual deficit, microcephaly, and dysmorphisms. IGF1RS may be caused by genomic or genetic defects affecting the IGF1R locus (15q26.3).Objective and hypotheses: Case report: a girl born at 36.5 weeks, BW 1.935 g (−3.2 SDS), length 41 cm (−4.4 SDS) and...

hrp0097p1-43 | Diabetes and Insulin | ESPE2023

Our experience in neonatal diabetes mellitus: clinical and molecular characterisation

Salamanca Fresno Luis , Gomes Porras Mariana , Pozo Román Jesús , Del Pozo Ángela , Rodríguez Jiménez Carmen , González Casado Isabel , Campos Barros Ángel

Introduction: Neonatal Diabetes Mellitus (NDM) is characterised by severe hyperglycaemia, usually diagnosed in the first 6 months of life. Genetic diagnosis helps distinguishing between its different causes and between transient (TNDM) and permanent (PNDM) forms, with repercussions on the therapeutic approach and follow-up.Aim: Clinical and molecular characterisation of a series of NMD cases under endocrinological follow...

hrp0082p2-d1-450 | Growth | ESPE2014

Identification of NPR2 Mutations in Disproportionate Short Stature

Hisado-Oliva Alfonso , Benito-Sanz Sara , Belinchon Alberta , Vallespin Elena , del Pozo Angela , Barreda-Bonis Ana C. , Ramirez Joaquin , Luzuriaga Cristina , Gonzalez-Casado Isabel , Campos-Barros Angel , Heath Karen E.

Background: Homozygous natriuretic peptide receptor-2 (NPR2) mutations cause acromesomelic dysplasia, type Maroteaux, a skeletal dysplasia with extreme disproportionate short stature and recently, heterozygous NPR2 mutations have been identified also in patients with idiopathic short stature (ISS, 2–6%). SHOX mutations are found in ~2–5% of ISS cases and ~70% of Léri-Weill dyschondrosteosis (LWD) cases, characterized by disproportionat...

hrp0084p2-459 | Growth | ESPE2015

Heterozygous NPR2 Mutations Cause Disproportionate Short Stature, Similar to Léri-Weill Dyschondrosteosis

Hisado-Oliva Alfonso , Garre-Vazquez Ana Isabel , Santaolalla-Caballero Fabiola , Belinchon Alberta , Barreda-Bonis Ana Coral , Vasques Gabriela A , Ramirez Joaquin , Luzuriaga Cristina , Gonzalez-Casado Isabel , Benito-Sanz Sara , Jorge Alexander A , Campos-Barros Angel , Heath Karen E

Background: Mutations in SHOX or its regulatory regions have been detected in ~70% of Léri-Weill dyschondrosteosis (LWD) and ~2.5% of idiopathic short stature (ISS) cases, suggesting the implication of other genes or loci. Recent studies have identified NPR2 defects in ISS patients.Objective and hypotheses: To investigate if NPR2 mutations can account for a proportion of the cases referred for LWD and ISS in whom no SHOX/PAR1 mutation was detected.<...

hrp0097rfc4.4 | Growth and syndromes (to include Turner syndrome) | ESPE2023

Genetic findings in short Turkish children born to consanguineous parents

Joustra Sjoerd , Isik Emregul , M. Wit Jan , Catli Gonul , Anik Ahmet , Haliloglu Belma , Kandemir Nurgun , Ozsu Elif , Hendriks Yvonne , de Bruin Christiaan , Kant Sarina , Campos-Barros Angel , Challis Rachel , Parry David , Harley Margaret , Jackson Andrew , Losekoot Monique , van Duyvenvoorde Hermine

Objective: To describe clinical, laboratory and genetic characteristics of 42 short children from 34 consanguineous Turkish families.Design: Descriptive case series.Methods: After collecting clinical information, DNA samples were analysed in three European laboratories. In 18 children (12 families) suspected of a genetic defect in the growth hormone (GH)-insulin-like growth factor ...

hrp0097rfc14.5 | Late Breaking | ESPE2023

Functional demonstration that variants in the C-terminal of IHH cause short stature and/brachdactyly

Diaz-González Francisca , Modamio-Høybjør Silvia , Lucas-Castro Elsa , Coral Barreda-Bonis Ana , Campos-Barros Angel , González-Casado Isabel , Sentchordi-Montané Lucia , E. Heath Karen

Introduction: Variants in the N-terminal of the Indian-hedgehog gene (IHH) have been associated with Brachydactyly type-A1 (AD) and Acrocapitofemoral dysplasia (AR), only three of which have been functionally studied. However, heterozygous IHH variants, majority classified as variants of unknown significance (VUS) are being increasingly identified, not only in the N-terminal but also in the uncharacterized C-terminal, by NGS, in individuals with short...

hrp0095rfc8.1 | Diabetes and Insulin | ESPE2022

Clinical Spectrum of HNF4A-mody (Mody1): From Neonatal Hyperinsulinism to Diabetes in Adults

Salamanca Fresno Luis , Itza Martín Nerea , Gomes Porras Mariana , Guerrero Fernández Julio , Ramírez Fernández Joaquin , Abad López Ainhoa , Solís López Mariano , Rodríguez Jiménez Carmen , Lía Nattero Chavez María , Alvarez Escolá Cristina , González Casado Isabel , Campos Barros Ángel

Background and Aims: HNF4A-MODY clinical expression is broad, ranging from hypoglycemic hyperinsulinism in the neonatal period and early childhood to hyperglycemia and diabetes, as insulin secretion progressively decreases in adult patients. The main objective was to clinically and molecularly characterize patients with glycemic alterations, negative autoimmunity and confirmed molecular diagnosis of HNF4A-MODY.Materials and Metho...

hrp0095p1-554 | Pituitary, Neuroendocrinology and Puberty | ESPE2022

Oligogenic Inheritance May Explain The Phenotypic Variability and Incomplete Penetrance of Deleterious GL1I2 Variants in Congenital Hypopituitarism

Javier Rodríguez-Contreras Francisco , Ros-Pérez Purificación , Amalia García de Santiago Fe , Regueras-Santos Laura , Ruiz-Cano Rafael , Vallespín Elena , Del Pozo Ángela , Solís Mario , Elise Heath Karen , González-Casado Isabel , Campos-Barros Ángel

Background: GL1I2 encodes a zinc-finger transcription factor expressed in the developing hypothalamus and in Rathke's pouch, the embryonic precursor of the pituitary gland. Pathogenic GL1I2 variants have been implicated in the etiology of the broad clinical spectrum of congenital hypopituitarism (CHY): holoprosencephaly, midline facial abnormalities, Culler-Jones syndrome, combined pituitary hormone-deficiency (CPHD) and isolated GH-defi...

hrp0089p1-p143 | GH &amp; IGFs P1 | ESPE2018

Severe Pre- and Postnatal Growth Retardation in a Child Harboring a Novel Homozygous IGF1 Gene Mutation

Claudia Keselman Ana , Alejandra Scaglia Paula , Martin Ayelen , Armando Romina , Maria Sanguineti Nora , Gutierrez Mariana , Braslavsky Debora , Gabriela Ballerini Maria , Gabriela Ropelato Maria , Cassinelli Hamilton , Casali Barbara , Del Rey Graciela , Campos Barros Angel , Nevado Blanco Julian , Domene Horacio , Jasper Hector , Arberas Claudia , Rey Rodolfo , Pennisi Patricia , Lapunzina-Badia Pablo , Bergada Ignacio

Background: Human IGF1 gene defects are characterized by intrauterine and postnatal growth retardation, sensorineural deafness, microcephaly and intellectual disability. Seven cases have been reported so far, and the underlying pathophysiology has been characterized in only three.Objective: To describe a patient with severe short stature presenting a novel homozygous IGF1 gene mutation and its underlying pathogenic mechanism.<p clas...