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...

hrp0084p1-64 | DSD | ESPE2015

MAMLD1 Mutations Seem Not Sufficient to Explain a 46, XY DSD Phenotype. What else?

Camats Nuria , Fernandez-Cancio Monica , Audi Laura , Mullis Primus E , Moreno Francisca , Casado Isabel Gonzalez , Lopez-Siguero Juan Pedro , Corripio Raquel , de la Vega Jose Antonio Bermudez , Blanco Jose Antonio , Fluck Christa E

Background: The MAMLD1 gene (Xp28) is thought to cause disorder of sex development (DSD) in 46, XY patients, mostly presenting with hypospadias, and, recently, also gonadal dysgenesis. However, there is some controversy about the role of MAMLD1 in sex development because i) some MAMLD1 variants are also detected in normal individuals, ii) others are not present in all affected DSD individuals of the same family; iii) several MAMLD1 mutations...

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.<...

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...

hrp0082fc4.1 | Growth | ESPE2014

Heterozygous IGF1R Mutations Represent a Frequent Finding in Patients with Pre- and/or Postnatal Proportional Undergrowth and Low, Normal or Supranormal IGF1

Campos-Barros Angel , Gomez-Nunez Ana , Gonzalez-Casado Isabel , Salamanca-Fresno Luis , Garcia-Minaur Sixto , Ros-Perez Purificacion , Borras-Perez Victoria , Audi Laura , Rosell-Andreo Jordi , de Sotto-Esteban Diego , Garcia-Cuartero Beatriz , Gonzalez-Vergaz Amparo , Cruz-Rojo Jaime , Garzon Lucia , Gallego-Gomez Elena

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: To investigate the frequency of IGF1R mutations in a cohort of patients with pre- and/or postn...

hrp0084fc2.3 | Bone &amp; Mineral Metabolism | ESPE2015

High Success of a Next Generation Sequencing Panel for the Molecular Diagnosis of Rare Skeletal Dysplasias

Barreza Jimena , Rivera-Pedroza Carlos I , Sentchordi-Montane Lucia , Vallespin Elena , Montano Victoria E F , Mansilla Elena , Belinchon Alberta , Benito-Sanz Sara , del Pozo Angela , Ibanez Kristina , Gonzalez-Casado Isabel , Guillen-Navarro Encarna , Prieto Pablo , del Pozo Jaime Sanchez , Cruz-Rojo Jaime , Galan Enrique , Lapunzina Pablo , Garcia-Minaur Sixto , Santos-Simarro Fernando , Heath Karen E

Background: A total of 456 skeletal dysplasias have been classified by molecular, biochemical and/or radiological criteria, into 40 groups. Despite this, the precise, final diagnosis is often difficult due to the high phenotypic and genotypic variability.Objective: To improve the molecular and clinical diagnosis of skeletal dysplasias using a custom-designed next-generation sequencing (NGS) panel.Method: A total of 56 skeletal dysp...

hrp0084p1-97 | Growth | ESPE2015

High Frequency of Hypomorphic Allelic Haplotypes of the gh1 Proximal Promoter in Patients with Proportional Undergrowth and Isolated GH Deficiency

Campos-Barros Angel , Gomez-Nunez Ana , Zurita-Munoz Olga , Gallego-Gomez Elena , Cruz-Rojo Jaime , Garzon Lucia , Luzuriaga-Tomas Cristina , Riano-Galan Isolina , Bezanilla-Lopez Carolina , Donate-Legaz Jose Maria , Marban-Calzon Mercedes , Ruperez Sara , Hermoso Florinda , Lara-Orejas Emma , Borras-Perez Ma Victoria , Rius-Peris Jose Manuel , Garcia-Cuartero Beatriz , Gonzalez-Casado Isabel

Background: Although isolated GH deficiency (IGHD) is one of the most frequent causes of postnatal proportional undergrowth, up to 85–90% of IGHD cases are still classified as idiopathic. On the other hand, previous reports identified up to 40 different GH1 proximal promoter haplotypes, some of which show hypomorphic effects, significantly reducing GH1 expression levels.Objective and hypotheses: To investigate the frequency of ...