NGS implementation in a paediatric public hospital for the diagnosis of genetic endocrine disorders: preliminary results using clinical exome

VILLEGAS, FLORENCIA; IZQUIERDO, AGUSTÍN; BÁRBARA CASALI; ROSENBROCK, SOLANGE; FREIRE, ANALÍA; GRINSPON, ROMINA; ARCARI, ANDREA; PATRICIA PAPENDIECK; MARINA SZLAGO; CLAUDIA ARBERAS; MARÍA GABRIELA ROPELATO; PAULA ALEJANDRA SCAGLIA; ARGUELLES, CELESTE; GABRIELA SANSÓ; SEBASTIÁN CASTRO; NORA SANGUINETI; ENACAN ROSA; ANA KESELMAN; ANA VIEITES; ROMINA ARMANDO; BALLERINI, MARÍA GABRIELA; IGNACIO BERGADA; ESNAOLA AZCOITI, MARÍA; ARIEL BERENSTEIN; BRUNELLO, FRANCO; LUCIANA BRENZONI; DEBORA BRASLAVSKY; FLORENCIA CLÉMENT; MIRTA GRYNGARTEN; ANA CHIESA; MARÍA DEL CARMEN FERNÁNDEZ; MARCELO MARTÍ; RODOLFO REY

Merida

Congreso; XXIX Congreso de la Sociedad Latinoamericana de Endocrinología Pediátrica; 2020

Sociedad Latinoamericana de Endocrinología Pediátrica

Introduction: Access to genetic diagnoses in our institutionwas restricted to a reduced group of endocrine disorders studiedin the context of research projects. The advent of Next GenerationSequencing (NGS) has allowed the development of effective highperformancediagnosis algorithms for genetic pediatric diseases.Objective: To implement the use of NGS sequencing technologyto meet the genetic testing needs for monogenic paediatric endocrine diseases and to evaluate diagnostic efficiency in a tertiarypublic Hospital.Material and methods: Patients with suspicion of rare geneticendocrine or metabolic diseases were included. DNA from peripheralblood was obtained from the patients and their parents. Thisstudy was approved by institutional review board. Genetic diagnosisand counselling process involved the following steps:1-Pregenetic: clinical evaluation by paediatric endocrinologistsand geneticists, selection of genetic testing strategy, informed consent.2-Genetictesting: performed by NGS (Clinical exome, Tru-Sight One, NextSeq 500, Illumina), analysed by own designedbioinformatic pipelines, variant prioritization (B-platform, Bitgenia)and classification (ACMG criteria), Sanger sequencing confirmationand family segregation. 3-Post genetic testing: Report,counselling and individualized follow up of the patient andfamily.Results: From March 2018 to July 2020, 83 probands were included(14 abnormalities of growth, 37 gonadal axis disorders, 13thyroid disorders, 5 neuroendocrine hereditary cancer, 6 phenylketonuria,3 galactosemia and 5 other endocrine abnormalities).Twenty-four were positive tests, with relevantvariants in a generelated to phenotype with appropriate familial segregation study(20 pathogenic, 9 likely pathogenic, 1 VUS). 12 cases are still underinvestigation, requiring further evidence (only one variant in a recessivegene, segregation pending, VUS). In 47 cases no variantsassociated to phenotype were found. Global diagnostic efficiencyis 28,9% (24/83).Conclusions: Interdisciplinary teamwork has enabled the successfulimplementation of new genomic diagnosis technologies inBuenos Aires public health system, achieving 28,9% diagnostic efficiencythat is consistent with bibliography. NGS platform is flexibleenough to fulfil the needs of a specialized paediatric centre.