ESPE Abstracts

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 ...

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...

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...

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...

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...

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...

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...

Background: Hematocolpos is a rare condition in young girls that can be caused by imperforated hymen or vaginal agenesis. It is usually diagnosed at early puberty with cyclic abdominal pain and amenorrhoea. Menarche is usually observed two years after the start of puberty; sometimes pre-menarcheal bleeding can occur, ranging from isolated premature menarche to spotting in course of puberty. In case of imperforated hymen or vaginal anomaly, a pre-menarcheal uterine bleeding can...

Background: Pseudohypoparathyroidism (PHP) encompasses a group of rare disorders defined by target organ unresponsiveness to parathyroid hormone (PTH). Patients with PHP type 1A carry heterozygous mutations of the maternal GNAS gene that encodes the α-subunit of the G protein. This protein is coupled to the PTH receptor as well as to other heptahelical receptors - TSH, GHRH and gonadotropins receptors.Objective and hypotheses: To describe a...

Background: Little is known about the long-term social outcome of diabetic children.Objective and hypotheses: This study aimed to describe social and professional life, quality of life (QOL) and sexuality at adult age of children and adolescents with type 1 diabetes (T1D).Method: Participants (n=388, age=28.5±3.1 years; duration of diabetes=17.0±2.7 years, recruited from a French national register) completed a qu...