hrp0089rfc7.1 | Fetal, Neonatal Endocrinology and Metabolism | ESPE2018

Next Generation Sequencing Results in 142 Patients with Congenital Hyperinsulinism

Gubaeva Diliara , Melikyan Maria , Vasiliev Eugeny , Petrov Vasily , Tiulpakov Anatoly

Congenital hyperinsulinism (CHI) is a life-threatening disorder characterized by hypoglycemia due to dysregulated secretion of insulin from pancreatic β-cells. Genetic diagnosis is essential for patient management. NGS technologies give the ability to generate large amounts of sequence data in a relatively short amount of time. We report next generation sequencing (NGS) results in 142 patients (66 boys, 76 girls) with CHI seen at Endocrine Research Centre (Moscow...

hrp0089p3-p051 | Bone, Growth Plate & Mineral Metabolism P3 | ESPE2018

Clinical and Genetic Evaluations of Three Patients with Vitamin D Dependent Rickets Type 1A

Kulikova Kristina , Kolodkina Anna , Vasiliev Eugeny , Petrov Vasily , Tiulpakov Anatoly

Vitamin D dependent rickets type 1A (VDDR-IA) is inherited in an autosomal recessive pattern and caused by mutations in CYP27B1 gene encoding enzyme 1α-hydroxylase. Deficiency of 1α-hydroxylase leads to decrease of 1,25(OH)2 vitamin D production. VDDR-IA usually manifests clinically during the 1st year of life. Clinical features of VDDR- IA include progressive growth retardation, hypotonia, rachitic skeletal deformities, hypocalcemic seizures in early infancy. Serum ...

hrp0092fc11.4 | Pituitary, Neuroendocrinology and Puberty Session 2 | ESPE2019

Whole Exome Sequencing in a Familial Case of Adamantinomatous Craniopharyngioma Revealed Two Hits Affecting Wnt-Signaling Pathway

Gorelyshev Alexander , Mazerkina Nadezhda , Vasilyev Evgeny , Petrov Vasily , Ryzhova Marina , Gorelyshev Sergey , Tiulpakov Anatoly

Background: Craniopharyngiomas (CPs) are benign brain tumours that intimately involve pituitary and, often, hypothalamus. Here, primary clinical conundrum is choosing between gross total resection and preserving endocrine functions. Robust predictors of recurrence are much needed, but require a deeper understanding of the molecular basis of CPs. Multiple studies show that CTNNB1 (β-catenin) somatic mutations drive the adamantinomatous subtype ...

hrp0092p1-332 | Diabetes and Insulin (2) | ESPE2019

Targeted Next-Generation Sequencing Demonstrates High Frequency of MODY in Russian Children.

Zubkova Natalia , Laptev Dmitry , Sorokin Daniil , Makretskaya Nina , Petrov Vasily , Vasilyev Evgeny , Tiulpakov Anatoly

Background: Maturity-onset diabetes of the young (MODY) is a heterogeneous group of disorders characterised by autosomal dominant type of inheritance and caused by genetic defects leading to dysfunction of pancreatic beta-cells. At least 13 types of MODY have been described in the literature, the most frequent of which are MODY types 1–3. The frequency of different MODY types in children in Russia has not been studied before.<strong...

hrp0084fc3.2 | Diabetes | ESPE2015

Experience with Molecular Diagnosis in 48 Cases of Neonatal Diabetes Mellitus Using Targeted Next-Generation Sequencing

Tikhonvich Yulia , Vasilyev Evgeny , Petrov Vasily , Malievsky Oleg , Petryaikina Elena , Ribkina Irina , Stotikova Olga , Tiulpakov Anatoly

Background: Neonatal diabetes mellitus (NDM) comprises a group of monogenic disorders caused by mutations in genes involved in pancreatic development or insulin secretion. Accurate and rapid molecular diagnosis of NDM is pivotal for making decision on the treatment strategy. Next-generation sequencing (NGS) allows simultaneos analysis of several candidate genes, which facilitates the diagnostic procedure in NDM.Objective and hypotheses: To summarise our ...

hrp0084p1-151 | Miscelleaneous | ESPE2015

A Case of Autoimmune Polyglandular Syndrome Type I Presenting as Progressive Generalised Lipodystrophy in a 15-month-old Child

Sorkina Ekaterina , Frolova Elena , Rusinova Dina , Polyakova Svetlana , Vasilyev Evgeny , Petrov Vasily , Tiulpakov Anatoly

Background: Autoimmune polyglandular syndrome type 1 (APS1) is a monogenic autoimmune disease caused by defects in autoimmune regulator gene (AIRE). The classic clinical triad is composed of Addison disease, hypoparathyroidism, and chronic mucocutaneous candidiasis, however other endocrine and non-endocrine features of APS1 may occur.Objective: To describe an unusual clinical manifestation of APS1.Methods: Congenital lipodystrophy ...

hrp0084p1-114 | Puberty | ESPE2015

Screening of Mutations in Idiopathic Hypogonadotropic Hypogonadism Using a Targeted Next-Generation Sequencing Approach

Kolodkina Anna , Kareva Maria , Kalinchenko Natalia , Raygorodskaya Nadezhda , Malievsky Oleg , Fidelina Olga , Vasilyev Evgeny , Petrov Vasily , Naumova Maria , Tiulpakov Anatoly

Background: To date at least 30 genes are known to be associated with idiopathic hypogonadotropic hypogonadism (IHH). Analysis of all these gene candidates by Sanger sequencing would be expensive, labour-intensive and time-consuming. Recent introduction of next-generation sequencing (NGS) enables simultaneous analysis of multiple gene targets making it an attractive approach in such conditions as IHHObjective and hypotheses: To study the spectrum of mole...

hrp0084p2-217 | Bone | ESPE2015

The Spectrum of Molecular Defects in 64 Patients with Hypophosphatemic Rickets Identified by Targeted Next-Generation Sequencing

Kulikova Kristina , Kolodkina Anna , Vasilyev Evgeny , Petrov Vasily , Gofman Fedor , Horkin Anatoly , Kenis Vladimir , Petrov Michael , Tiulpakov Anatoly

Background: Hypophosphatemic rickets (HR) comprises a group of inherited forms of rickets characterised by renal phosphate wasting. To date more than 10 genes are associated with HR, and a comprehensive molecular diagnosis in these disorders is technically difficult to perform.Objective and hypotheses: To assess the value of targeted next-generation sequencing (NGS) used for molecular analysis of candidate genes of HR.Method: 64 pa...

hrp0084p2-294 | Diabetes | ESPE2015

The Prevalence of Different Subtypes of Maturity-Onset Diabetes of the Young in Russian Federation as Defined by Targeted Next-Generation Sequencing

Zubkova Natalya , Gioeva Olesya , Tichonovich Yulia , Petrov Vasily , Vasilyev Evgeny , Malievsky Oleg , Kiyaev Alexey , Timofeev Alexey , Tiulpakov Anatoly

Background: Among the currently known variants of maturity-onset diabetes of the young (MODY) subtypes 1–3 are the most prevalent, while their relative frequencies vary in different populations. Other types of MODY are more rare, although the studies addressing their prevalences are limited. Recent implementation of next-generation sequencing (NGS) enables simultaneos analysis of multiple candidate genes making it an attracive approach in various monogenic disorders, incl...

hrp0084fc13.3 | Thyroid | ESPE2015

Targeted Next-Generation Sequencing Demonstrates High Frequency of ‘Dyshormonogenesis Genes’ Mutations in Severe Congenital Hypothyroidism

Makretskaya Nina , Bezlepkina Olga , Kolodkina Anna , Kiyaev Alexey , Vasilyev Evgeny , Petrov Vasily , Kalinenkova Svetlana , Duhoreva Olga , Malievsky Oleg , Dedov Ivan , Tiulpakov Anatoly

Background: 80–85% of cases of congenital hypothyroidism (CH) are shown to be due to thyroid dysgenesis, while 15–20% are due to dyshormonogenesis. At least 12 candidate genes are associated with congenital hypothyroidism (CH), however its molecular basis is defined in fewer than 10% of the patients (ESPE consensus, 2014). Recent studies suggest that using a next generation sequencing (NGS) approach may increase the mutation yield in CH.Objecti...