hrp0092rfc3.3 | Multi-system Endocrine Disorders | ESPE2019

The Founder Homozygous NR5A1 Gene Mutation p.R103Q Causes Asplenia and Severe XY-DSD and XX-DSD in a Palestinian Cohort

Abdulhadi-Atwan Maha , Hidesh Guy , Abulibdeh Abdulsalam , Hirsch Harry , Klopstock Tehila , Levy-Lahad Ephrat , Zangen David

Background: Mutations in Steroidogenic factor 1 (SF-1; also known as NR5A1), a transcription factor involved in sexual differentiation, steroidogenesis and reproduction, have been associated with mild to severe XY and XX DSDs and adrenal failure. Asplenia and complete XY sex reversal were recently reported in a Palestinian patient homozygous for p.R103Q NR5A1 mutation.Clinical Cases: Five Pales...

hrp0089p2-p299 | Multisystem Endocrine Disorders P2 | ESPE2018

The N309K Pro-Protein Convertase Type 1 (PCSK1) Gene Mutation Causes Lack of Spontaneous Puberty and Primary Amenorrhea

Abdulhag Ulla Najwa , Sharaf Mona , Libdeh Abdulsalam Abu , Zangen David

Introduction: PCSK1/3 gene mutations are known as a cause for congenital diarrhea and various endocrinopathies. Hypogonadotrophic hypogonadism and aberrant pubertal development due to pro-convertase dysfunction was not characterized yet. This study aimed to characterize the pubertal development in a family carrying the novel N309K mutation in the PCSK1 gene.Methods and Results: We Identified 2 siblings who presented with severe congenital diarrhea follow...

hrp0092fc11.3 | Pituitary, Neuroendocrinology and Puberty Session 2 | ESPE2019

A Novel Genetic Aetiology for Familial Neonatal Central Diabetes Insipidus

lavi Eran , Sharaf Muna , Abu-Libdeh Abdulsalam , Renbaum Pinchas , Levy-Lahad Ephrat , Zangen David

Background: Central diabetes insipidus (CDI) in the neonatal age is usually a result of intracranial insult, either congenital or acquired. Familial CDI is usually an autosomal dominant disorder, presenting later in childhood (1-6 y) with polyuria and mostly caused by mutations in the Neurophysin II moiety of the AVP-NPII prohormone gene; these interfere with prohormone processing leading to gradual destruction of AVP secreting cells and result in arginine vas...

hrp0089rfc2.6 | Bone, Growth Plate & Mineral Metabolism 1 | ESPE2018

The Novel R211Q POP1 Homozygous Mutation Causes Severe Short Stature But Uniquely Only Subtle Skeletal Dysplasia

Abdulhadi-Atwan Maha , Klopshtock Tehila , Sharaf Muna , Weinberg-Shokrun Ariella , Levy-Lahad Ephrat , Zangen David

Background: Processing of Precursor 1 (POP1) is a core protein component of the Ribonuclease-Mitochondrial RNA Processing (RNase-MRP) enzymatic complex, an essential complex in all eukaryotes. Mutations in RMRP, encoding the RNA moiety of the complex cause cartilage-hair hypoplasia – anauxetic dysplasia (CHH-AD) spectrum disorders, characterized by severe disproportionate short stature. Recently, five patients harboring mutations in POP1 have been report...

hrp0086rfc9.1 | Pathophysiology of Disorders of Insulin Secretion | ESPE2016

Neonatal Diabetes due to NKX2.2 Mutation – Genotype, Clinical Phenotype and Therapeutic Challenges in a Very Low Birth Weight Diabetic Neonate

Auerbach Adi , Shlomai Noa Ofek , Shokrun Ariella Weinberg , Levy-Lahad Ephrat , Zangen David

Background: Insulin treatment in a very low birth weight neonate having persistent hyperglycemia is challenging. The very recently reported novel human genetic cause of neonatal diabetes due to NKX2.2 pancreatic transcription factor mutations is associated with very low birth weight deliveries.Objective and hypotheses: To study the diagnostic process, the molecular genetics, the clinical phenotype, and the significant therapeutic challenges in the manage...

hrp0084p1-9 | Adrenal | ESPE2015

Founder Effect and the Clinical and Molecular Characteristics in a Cohort of Classical and Non-Classical Congenital Lipoid Adrenal Hyperplasia Due To StAR Mutations

Abu-Libdeh Abdulsalam , Shokrun Ariella Weinberg , Levy-Lahad Ephrat , Admoni Osnat , Tenenbaum-Rakover Yardena , Zangen David

Background: Classical and non-classical congenital lipoid adrenal hyperplasia (CLAH) are extremely rare condition caused by mutations in StAR. The degree of enzyme activity impairment determines the clinical phenotypes.Objective and hypotheses: To identify the genetic cause of primary adrenal insufficiency in a cohort of patients from 13 unrelated families with classical and non-classical CLAH, to correlate genotype to phenotype and to identify ...

hrp0094p1-184 | Pituitary B | ESPE2021

The pituitary gonadal axis is not responsive to GnRH administration in PCSK 1 dysfunction

Mendelsohn Espen Eliyahu , Lavi Eran , Cahn Ranit , Sharaf Muna , Abu Libdeh Abdulsalam , Zangen David ,

Introduction: Patients homozygous for mutation in the PCSK-1 gene present clinically with severe congenital diarrhea and variable hormonal defects due to lack of enzyme/prohormone processing by Prohormone Convertase 1/3 (PC1/3). Although absence of spontaneous puberty has been reported in patients with PCSK-1 mutations, no peptide hormone(s) in the hypothalamus-pituitary-gonadal axis (HPG) have been reported to be dependent on PC1/3 cleavage. Here we studied t...

hrp0092rfc10.6 | Sex Differentiation, Gonads and Gynaecology or Sex Endocrinology | ESPE2019

AA Mutation in the Nucleoporin-107 Gene Causes Aberrant Dpp/BMP Signaling and XX Gonadal Dysgenesis

Shorê Tikva , Levi^ Tgst , Kalifa Rachel , Rekler Dina , Dreifuss Amatzia , Weinberg-Shukron Ariella , Lavi Eran , Gerlitz Offer , Zangen David

Background: Though the genes and signalling pathways involved in sexual development have only been partially elucidated, it is known that their disruption can result in disorders of sexual development (DSD). XX ovarian dysgenesis (XX-OD) is a rare, genetically heterogeneous disorder characterized by underdeveloped and dysfunctional ovaries. We previously identified a novel missense mutation in Nucleoporin107 (Nup107, c.1339G>A, p.D447N), an essential compo...

hrp0086rfc6.8 | Syndromes: Mechanisms and Management | ESPE2016

The Actual Incidence of Small for Gestational Age (SGA) Newborns and their Catch-up Growth is Dramatically Lower than Previously Considered

Lavi Eran , Shafrir Asher , Libdeh Abdulsalam Abu , Stein-Zamir Chen , Friedman Smadar Eventov , shoob Hanna , Zangen David Haim

Background: SGA is defined as birth weight under 2 standard deviations (SD) from the mean. Previous studies indicate that 10% of SGA babies do not have “catch-up growth” (CUG). They are eligible for growth hormone (GH) therapy to increase final height. The unexpected low demand for GH therapy in SGA babies, triggered us to survey the actual incidence of SGA and failure in CUG.Objective and hypotheses: To find the actual incidence of SGA and fai...

hrp0086p1-p349 | Gonads & DSD P1 | ESPE2016

Severe 5 Alpha Reductase 2 Deficiency with Aphallia is Caused by p.Y91H SRD5A2 Mutation and is Responsive to Dihydrotestosterone Administration During Childhood

Auerbach Adi , Weinberg Shokrun Ariella , Abdelhak Najwa , Lavi Eran , Hidas Guy , Landau Yehezkel , Levy-Lahad Ephrat , Zangen David

Background: 5-alpha-reductase-2 (5α-RD2) deficiency is an autosomal recessive 46,XY disorder of sexual development, characterized by undervirilized prepubertal males with ambiguous genitalia. The pubertal rise in testosterone and 5α-RD1 isoenzyme activity causes virilization, often resulting in gender assignment change. Early precise diagnosis which anticipate adult function is critical for treatment and gender assignment.Objective and hypothes...