hrp0095p1-452 | Diabetes and Insulin | ESPE2022

Limited genotype-phenotype correlation in FOXP3 gene within same family member

Sharaf Muna , Alaaraj Nada , Shurrab Shaymaa , Zangen David

Introduction: FOXP3 protein is crucial in enabling T-regulatory cells to maintain tolerance to self-antigens. Mutations in human Foxp3 gene are associated with immune diseases, such as multi-organ autoimmune disorder, immune dysregulation, polyendocrinopathy, enteropathy and X-linked syndrome (IPEX).Case Presentation: A 15 months old male, presented initially at 2 weeks of age with failure to thrive hyperglycemia and sev...

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...

hrp0097rfc10.6 | Fetal, neonatal endocrinology and metabolism (to include hypoglycaemia) & Multisystem endocrine disorders | ESPE2023

Two novel mutations in the DCAF17 gene in two Palestinian families with primary amenorrhea revealing molecular genetics in Woodhouse-Sakati syndrome & unique presentation

Abu-Libdeh Abdulsalam , Florsheim Natan , Eideh Hasan , Zangen David

Background: Woodhouse-Sakati syndrome (WSS) is an extremely rare autosomal recessive multisystem disease. Ectodermal system findings, such as alopecia and changes in facial skin, endocrinological problems including hypogonadism, hypothyroidism, diabetes mellitus (DM), and decreased levels of insulin-like growth factor I (IGF-I), neurological disorders such as hearing loss and progressive extrapyramidal involvement are the components of this syndrome. The syndr...

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 ...

hrp0095rfc5.6 | Adrenals and HPA Axis | ESPE2022

The unique methylation pattern of a rare Bilateral para-overian Adrenal Rest Tumor in a girl with severe virilization and Nicotinamide Nucleotide Transhydrogenase mutation

Cahn Ranit , Berman Ben , Bauman Dvorah , Mendelson Espen , Abulibdeh Abdulsalam , Florsheim Natan , Zangen David

Background: Patients with NNT (Nicotinamide Nucleotide Transhydrogenase) gene mutations, a rare cause of glucocorticoid and mineralocorticoid deficiency. Adrenal Rest Tumor (ART) in females, reported so far only in noncompliant patients with congenital adrenal hyperplasia and elevated ACTH levels, is very rare (<20 cases world-wide). This study characterizes the pathophysiology, the molecular ontogeny and methylation analysis of a unique ART in a female wit...

hrp0095p1-175 | Sex Differentiation, Gonads and Gynaecology, and Sex Endocrinology | ESPE2022

Primary Ovarian Failure as a Result of Homozygous Mutations in MCM10 Gene

Landau Zohar , Florsheim Natan , Simon Itamar , Kramer Joyce , Renbaum Pinchas , Levy-Lahad Efrat , Zangen David

Background: Primary ovarian failure is (POF) characterised by primary amenorrhoea or early menopause in females. Minichromosome maintenance 10 (MCM10) is a gene involved in DNA damage repair, DNA replication and chromatin formation has received attention as a potential genetic etiology for neoplastic disease. Drosophila with mutated MCM10 have subfertility and dysfunction in female germline development. In humans, biallelic mutations of the MCM10 causes NK cel...

hrp0095p1-575 | Sex Differentiation, Gonads and Gynaecology, and Sex Endocrinology | ESPE2022

A novel mutation in the BMP15 gene in a Palestinian family with primary amenorrhea revealing molecular genetics of premature ovarian insufficiency

Abu-Libdeh Abdulsalam , Floresheim Natan , Renbaum Pinchas , Levy-Lahad Ephrat , Zangen David

Background: Severe XX-DSD and ovarian dysgenesis (OD) are the extreme clinical phenotype of approximately 1% of women that are affected by primary ovarian insufficiency (POI). BMP15 and GDF9 are two members of transforming growth factor ß (TGF-β) superfamily; they share an oocyte-specific expression pattern and play a crucial role in early folliculogenesis. Only XX cases of mutations in BMP15 have been proved to cause human disease. Here we describe...

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...

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...

hrp0089rfc2.6 | Bone, Growth Plate &amp; 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...