hrp0089fc4.4 | GH & IGFs | ESPE2018

A Cross-Sectional Study of IGF-I Bioavailability Through Childhood and Associations with PAPP-A2, STC2 and Anthropometric Data

Fujimoto Masanobu , Khoury Jane , Andrew Melissa , Hwa Vivian , Dauber Andrew

Background: Insulin-like growth factor I (IGF-I) is one of the important hormonal mediators of human growth. Circulating IGF-I exists in a ternary complex bound to the acid-labile subunit (ALS) and one of its six binding proteins (BPs). IGF-I bound to ALS and BPs needs to be liberated by either Pregnancy Associated Plasma Protease A (PAPP-A) or A2 (PAPP-A2) to reach its receptor. Stanniocalcin 2 (STC2) is a potent inhibitor of both PAPP-A and PAPP-A2. Genome-wide association s...

hrp0086fc8.3 | Growth: Clinical | ESPE2016

PAPP-A2 Gene Mutation Effects on Glucose Metabolism and Bone Mineral Density and Response to Therapy with Recombinant Human IGF-I

Salcedo Catalina Cabrera , Hwa Vivian , Tyzinski Leah , Andrew Melissa , Wasserman Halley , Backeljauw Philippe , Dauber Andrew

Background: PAPP-A2 (pregnancy-associated plasma protein A2) deficiency, caused by homozygous mutations in the PAPP-A2 gene results in a novel syndrome of significant growth failure. PAPP-A2 cleaves IGF binding proteins 3 and 5, thereby freeing IGF-I from its ternary complex and allowing it to become biologically active. We recently reported the first two families with PAPP-A2 mutations. Response to recombinant human IGF-I (rhIGF-1) in these patients is unknown.<p class="a...

hrp0086rfc14.3 | Growth : Mechanisms | ESPE2016

Whole Exome Sequencing Identifies a GH1 Gene Mutation Causing Familial Isolated Growth Hormone Deficiency with Normal Peak Growth Hormone Concentrations

Salcedo Catalina Cabrera , Hwa Vivian , Tyzinski Leah , Andrew Melissa , Backeljauw Philippe , Dauber Andrew

Background: Familial isolated growth hormone deficiency (IGHD) type II is autosomal dominantly inherited and caused by splice-site mutations and nucleotide substitutions in the GH1 gene. The missense mutation R183H is a well-described genetic variant that causes familial IGHD type II. Individuals with this mutation have releasable GH stores, but GH secretion is severely reduced resulting in short stature.Objective and hypotheses: This study aimed to repo...

hrp0097p1-112 | Growth and Syndromes | ESPE2023

Treatment of Short Stature in Aggrecan Deficient Patients with Recombinant Human Growth Hormone: Three-Year Growth Response

Muthuvel Gajanthan , Dauber Andrew , Alexandrou Eirene , Tyzinski Leah , Andrew Melissa , Hwa Vivian , Backeljauw Philippe

Background: Aggrecan (ACAN) is a proteoglycan found in the extracellular matrix of articular and growth plate cartilage. Animal studies have shown that mutations in the ACAN gene lead to premature hypertrophic chondrocyte maturation, causing accelerated cartilage ossification. Patients with ACAN deficiency present with dominantly inherited short stature, often with advanced skeletal maturation and premature growth cessation, as well as early-onset joint diseas...

hrp0086fc14.1 | Growth : Mechanisms | ESPE2016

Clinical Characterization of Children with Autosomal Dominant Short Stature due to Aggrecan Mutations Broadens the Phenotypic Spectrum

Gkourogianni Alexandra , Andrew Melissa , Crocker Melissa , Dunbar Nancy , Jorge Alexander , Lafranchi Stephen , Lalani Seema , Lebl Jan , Lin Lynda , Los Evan , Newbern Dorothee , Nowak Catherine , Olson Micah , Popovic Jadranka , Pruhova Stepanka , Quintos Jose Bernardo , Sentchordi Lucia , Baron Jeffrey , Nilsson Ola , Dauber Andrew

Background: Heterozygous mutations in the Aggrecan gene (ACAN) cause autosomal dominant short stature with bone age (BA) acceleration, and premature growth cessation.Objective and methods: To characterize the phenotypic spectrum, associated conditions and describe response to growth-promoting therapies, detailed clinical evaluation of 73 mutation positive individuals from 16 families different families with heterozygous ACAN mutations was perfor...