hrp0084fc13.1 | Thyroid | ESPE2015

Gain of Function STAT3 Mutation in a Boy with Early Onset Autoimmune Diabetes and Thyroid Disease, Prenatal and Postnatal Growth Impairment and Lymphoproliferation

Sediva Hana , Dusatkova Petra , Dusatkova Lenka , Sumnik Zdenek , Kolouskova Stanislava , Pruhova Stepanka , Lebl Jan

Background: Recently, a new monogenic cause of multiple immune system disorders and short stature has been attributed to germline activating mutations in the STAT3 gene encoding signal transducer and activator of transcription 3. Possible pathophysiological mechanisms include enhanced proliferation and activation of T-helper 17 cells and inhibition of regulatory T-cells by STAT3, as described in in vitro studies.Case presentation: The a...

hrp0084p2-491 | Hypo | ESPE2015

Functional Analysis of Novel ABCC8 Mutations Found in Czech Patients with Congenital Hyperinsulinism

Rozenkova Klara , Dusatkova Petra , Dusatkova Lenka , Nessa Azizun , Obermannova Barbora , Kytnarova Jitka , Sumnik Zdenek , Lebl Jan , Hussain Khalid , Pruhova Stepanka

Background: Congenital Hyperinsulinism (CHI) is a heterogeneous genetically determined condition that is characterised by unregulated secretion of insulin from pancreatic β-cells. The most common and severe cases are caused by mutations in the ABCC8 gene encoding the SUR1 subunit of the KATP channel subunit. To assess the pathogenic effect of novel ABCC8 mutations we performed in-vitro functional studies.Objective and hy...

hrp0082p2-d1-458 | Growth | ESPE2014

Two Duplications Within PAR1 in a Family With Idiopathic Short Stature

Obermannova Barbora , Drabova Jana , Dusatkova Petra , Lebl Jan

Background: Short stature homeobox-containing gene (SHOX) is located within the pseudoautosomal region 1 (PAR1) of the sex chromosomes. SHOX mutations and PAR1 deletions encompassing SHOX or its upstream/downstream enhancers have been identified in ~60% of Léri-Weill dyschondrosteosis (LWD) and ~5–15% of idiopathic short stature (ISS) patients. Recently SHOX duplications have been described in LWD/ISS individuals.Case presentation: The boy was ...

hrp0084p1-80 | Growth Hormone | ESPE2015

Good Clinical Response to the Growth Hormone Therapy in the Patient with Familiar Short Stature Caused by Novel p.Val478Serfs*14 Mutation in ACAN Gene and Isolated Growth Hormone Deficiency

Pruhova Stepanka , Dusatkova Lenka , Dusatkova Petra , Zemkova Dana , Lebl Jan

Background: Recently a heterozygote mutations in the gene ACAN coding the protein aggrecan has been described as a cause of familiar short starture combined with accelerated bone age. The aggrecan is an extracellular proteoglycan in cartilage of growth plates and plays an important role in biological and biomechanical properties of cartilage.Objective and hypotheses: To provide a genetic screening of ACAN within the families with familiar short stature a...

hrp0086p1-p229 | Diabetes P1 | ESPE2016

Phenotypic Variability of Identical Mutations in the ABCC8 Gene in Two Families

Rozenkova Klara , Zapletalova Jirina , Dusatkova Lenka , Dusatkova Petra , Obermannova Barbora , Pruhova Stepanka , Lebl Jan , Sumnik Zdenek

Background: Mutations in the SUR1 subunit of the KATP channel encoded by the ABCC8 gene can result in diverse phenotypes ranging from Transient Neonatal Diabetes (TNDM) to type 2 diabetes in adulthood. These patients may benefit from sulphonylurea treatment.Objective and hypotheses: To describe the course of diabetes in two families with ABCC8 gene mutations and to assess the effect of sulphonylurea treatment.<p class="ab...

hrp0082p1-d2-74 | Diabetes (1) | ESPE2014

Transient Hyperglycaemia Preceded by Neonatal Hyperinsulinaemic Hypoglycaemia in an Infant with a Novel HNF1A Mutation

Obermannova Barbora , Rozenkova Klara , Dusatkova Petra , Pruhova Stepanka , Sumnik Zdenek , Lebl Jan

Background: The phenotype associated with heterozygous HNF1A gene mutations has recently been extended to include neonatal hyperinsulinaemic hypoglycaemia (HH) in addition to maturity-onset diabetes of the young (HNF1A–MODY).Objective and hypotheses: The baby boy was born at 38th week of gestation; BW 4110 g; BL 53 cm (LGA). The mother had gestational diabetes; her father is treated for diabetes mellitus from the age of 50 years. The boy de...

hrp0082p2-d2-461 | Growth (1) | ESPE2014

Anophthalmia, Abnormal Pituitary Development, and Suboptimal Response to GH Therapy in Two Children With Microdeletions of 14q22q23

Dusatkova Petra , Slamova Zuzana , Sumnik Zdenek , Simandlova Martina , Zemankova Elsa , Sedlacek Zdenek , Lebl Jan

Background: Microdeletions of 14q22q23 have been associated with eye abnormalities. Other symptoms in deletion carriers are less well recognized.Objective and hypotheses: We focused on growth characteristics and response to GH treatment in two unrelated children with 14q22q23 deletions.Method: Array comparative genomic hybridisation (aCGH).Results: Both patients displayed bilateral anophthalmia. Their brain M...

hrp0094p1-56 | Bone B | ESPE2021

Chondrocyte regulating and other growth plate genes are invaluable growth regulators: a study on children with short stature from 55 consanguineous families

Anne Amaratunga Shenali , Tayeb Tara Hussein , Dusatkova Petra , Elbova Lenka , Pruhova Stepanka , Lebl Jan ,

Introduction: Statural growth is regulated by multiple genetic, epigenetic and environmental mechanisms. The GH-IGF-1 axis was long believed to be the main linear growth regulator in children until more recent studies showed that the complex regulation of growth plate chondrocytes play an equal role. In order to extend our knowledge about the genes involved in short stature, we studied a unique cohort of children with short stature from consanguineous families...

hrp0082p1-d1-183 | Perinatal and Neonatal Endocrinology | ESPE2014

Molecular Genetic Analysis of Czech Patients with Congenital Hyperinsulinism: Surprisingly High Incidence of HNF1A Mutations

Rozenkova Klara , Dusatkova Lenka , Dusatkova Petra , Kytnarova Jitka , Obermannova Barbora , Rypackova Blanka , Sumnik Zdenek , Lebl Jan , Cinek Ondrej , Pruhova Stepanka

Background: Congenital hyperinsulinism of infancy represents a group of heterogeneous disorders characterized by over-secretion of insulin from pancreatic β cells causing severe hypoglycemia. Genetically, congenital hyperinsulinism is caused by defects in key genes regulating insulin secretion (ABCC8, KCNJ11, GLUD1, GCK, HADH, SLC16A1, UCP2, HNF4A, and non-constantly HNF1A). The aim of our pr...

hrp0082p2-d2-337 | Diabetes (1) | ESPE2014

The Length of the Deletion in the Region 17q Contributes to the Individual Variability of the Phenotype of Patients with Renal Cysts and Diabetes Syndrome (RCAD, HNF1B-MODY)

Pruhova Stepanka , Dusatkova Petra , Malina Michal , Slamova Zuzana , Blahova Kveta , Kotalova Radana , Dusek Jiri , Lebl Jan , Seeman Tomas , Cinek Ondrej

Background: The renal cysts and diabetes (RCAD) syndrome caused by defects in the HNF1B is characterized by a broad spectrum of clinical features. While heterozygous point mutations are relatively rare, we focused on gross deletions of the HNF1B that are determined by multiplex ligation probe-dependent amplification (MLPA). Rather importantly, the deletions most often extend beyond the single HNF1B, thus more deleted genes may participate in the clin...