29th Annual Meeting, SLEP, Mérida, Mexico, December 2020: Abstracts

SCAGLIA PAULA; ARGUELLES CELESTE; SANSÓ GABRIELA E; CASTRO SEBASTIÁN; ESNAOLA AZCONTI MARIA; BERENSTEIN ARIEL; BRUNELLO FRANCO GINO; ROPELATO MARIA GABRIELA; VILLEGAS FLORENCIA; IZQUIERDO AGUSTÍN; CASALI BÁRBARA

Hormone research in paediatrics

NLM (Medline)

Año: 2021 vol. 93 p. 1 - 46

Introduction: Access to genetic diagnoses in our institutionwas restricted to a reduced group of endocrine disorders studied in the context of research projects. The advent of Next Generation Sequencing (NGS) has allowed the development of effective highperformance diagnosis algorithms for genetic pediatric diseases.Objective: To implement the use of NGS sequencing technology to meet the genetic testing needs for monogenic paediatric endocrine diseases and to evaluate diagnostic efficiency in a tertiary public Hospital.Material and methods: Patients with suspicion of rare genetic endocrine or metabolic diseases were included. DNA from peripheral blood was obtained from the patients and their parents. This study was approved by institutional review board. Genetic diagnosis and counselling process involved the following steps: 1-Pregenetic: clinical evaluation by paediatric endocrinologists and geneticists, selection of genetic testing strategy, informed consent. 2-Genetic testing: performed by NGS (Clinical exome, TruSight One, NextSeq 500, Illumina), analysed by own designed bioinformatic pipelines, variant prioritization (B-platform, Bitgenia) and classification (ACMG criteria), Sanger sequencing confirmation and family segregation. 3-Post genetic testing: Report, counselling and individualized follow up of the patient and family.Results: From March 2018 to July 2020, 83 probands were included (14 abnormalities of growth, 37 gonadal axis disorders, 13 thyroid disorders, 5 neuroendocrine hereditary cancer, 6 phenylketonuria, 3 galactosemia and 5 other endocrine abnormalities). Twenty-four were positive tests, with relevant variants in a gene related to phenotype with appropriate familial segregation study (20 pathogenic, 9 likely pathogenic, 1 VUS). 12 cases are still under investigation, requiring further evidence (only one variant in a recessive gene, segregation pending, VUS). In 47 cases no variants associated to phenotype were found. Global diagnostic efficiencyis 28,9% (24/83).Conclusions: Interdisciplinary teamwork has enabled the successful implementation of new genomic diagnosis technologies in Buenos Aires public health system, achieving 28,9% diagnostic efficiency that is consistent with bibliography. NGS platform is flexible enough to fulfil the needs of a specialized paediatric centre.