hrp0097p1-570 | Sex Differentiation, Gonads and Gynaecology, and Sex Endocrinology | ESPE2023

Elucidating The Genetic Basis of Human Disorders of Sex Development Using Clinic-To-Bench Approach

Florsheim Natan , Renbaum Paul , Levy-Lahad Ephrat , Zangen David

Background: Diseases of sex development (DSD) are rare heterogeneous disorders ranging from infertility (an estimated 15% of couples worldwide have difficulty conceiving), to severe cases including ambiguous genitalia, sex reversal, and gonadal dysgenesis. The genetic basis of DSD remains unknown in 50% of the severe cases. To identify novel genetic causes of DSD, we are investigating patients in which known causative genes have been excluded. Identifying new ...

hrp0095p1-179 | Sex Differentiation, Gonads and Gynaecology, and Sex Endocrinology | ESPE2022

Loss of function of FIGNL1, a DNA damage response gene, is a novel cause of human ovarian dysgenesis

Florsheim Natan , Naugolny Larisa , Renbaum Paul , Lobel Orit , Y. Gold Merav , Goldberg Michal , Levy-Lahad Ephrat , Zangen David

Background: Severe Ovarian Dysgenesis (OD), a rare heterogeneous XX disorder of Sex Development presents clinically with primary amenorrhea, hypergonadotrophic hypogonadism and infertility. The genetic basis of OD remains unknown in 70% of cases. To identify novel causes of OD, we study patients in which known genes have been excluded.Methods: Whole-exome-sequencing was performed in a 14.5y old Ashkenazi Jewish, non-cons...

hrp0082p1-d2-4 | Adrenals & HP Axis | ESPE2014

Mineralo and Glucocorticoid Deficiency in Early Infancy are Caused by a Founder Novel Mutation in the Nicotinamide Nucleotide Transhydrogenase Gene

Abu-Libdeh Abdulsalam , Weinberg-Shukron Ariella , Zeligson Sharon , Zhadeh Fouad , Carmel Liran , Renbaum Paul , Levy-Lahad Ephrat , Zangen David

Background: Nicotinamide nucleotide transhydrogenase (NNT) gene mutations have been recently shown to cause familial glucocorticoid deficiency (FGD), by decreasing reactive oxygen species (ROS) detoxification in adrenocortical cells. Affected infants present within the first few months with isolated glucocorticoid deficiency.Objective and Hypotheses: To study the genetic etiology of four cases presenting uniquely with neonatal addisonian crisis (both min...

hrp0092p1-128 | Sex Differentiation, Gonads and Gynaecology or Sex Endocrinology | ESPE2019

The Novel Founder Homozygous V225M Mutation in the 17HSDB3 Gene Causes Aberrant Splicing and Severe XY-DSD

Levy-Khademi Floris , Zeligson Sharon , Klopstock Tehila , Chertin Boris , Avnon-Ziv Carmit , Renbaum Paul , Lavi Eran , Sharaf Muna , Perlman Shira , Behar Doron , Zahade Fouad , Levy-Lahad Ephrat , Zangen David , Segel Reeval

Background: Mutations in the gene HSD17B3 encoding the 17-beta hydroxysteroid dehydrogenase 3 enzyme cause testosterone insufficiency leading to XY DSD. In this study the clinical characteristics and molecular etiology of 3 new severe XY DSD cases from consanguineous families are elucidated.Clinical report: Three female patients (2 sisters and a single unrelated female) presented at ages 0.1, 8 and 0.7 years with ambiguo...