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Diagnostic power and clinical impact of exome sequencing in a cohort of 500 patients with rare diseases
Author(s) -
Quaio Caio Robledo D'Angioli Costa,
Moreira Caroline Monaco,
NovoFilho Gil Monteiro,
SacramentoBobotis Patricia Rossi,
Groenner Penna Michele,
Perazzio Sandro Felix,
Dutra Aurelio Pimenta,
Silva Rafael Alves,
Santos Monize Nakamoto Provisor,
Arruda Vanessa Yurie Nozaki,
Freitas Vanessa Galdeno,
Pereira Vinícius Ceola,
Pintao Maria Carolina,
Fornari Alexandre Ricardo dos Santos,
Buzolin Ana Lígia,
Oku Andre Yuji,
Burger Matheus,
Ramalho Rodrigo Fernandes,
Marco Antonio David Santos,
Ferreira Elisa Napolitano,
Pereira Otavio Jose Eulalio,
Cantagalli Vanessa Dionisio,
Trindade Ana Carolina Gomes,
Sousa Rafaela Rogerio Floriano,
Reys Furuzawa Cintia,
Verzini Fernanda,
Matalhana Shirley Dezan,
Romano Naiade,
Paixão Daniele,
Olivati Caroline,
Spolador Gustavo Marquezani,
Maciel Gustavo Arantes Rosa,
Rocha Viviane Zorzanelli,
Miguelez Javier,
Carvalho Mario Henrique Burlacchini,
Souza Alexandre Wagner Silva,
Andrade Luis Eduardo Coelho,
Chauffaille Maria de Lourdes,
Perazzio Aline dos Santos Borgo,
Catelani Ana Lucia Pereira Monteiro,
MitneNeto Miguel,
Kim Chong Ae,
Baratela Wagner Antonio da Rosa
Publication year - 2020
Publication title -
american journal of medical genetics part c: seminars in medical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.419
H-Index - 101
eISSN - 1552-4876
pISSN - 1552-4868
DOI - 10.1002/ajmg.c.31860
Subject(s) - cohort , medicine , exome sequencing , pediatrics , disease , cohort study , exome , genetics , mutation , biology , gene
Rare diseases comprise a diverse group of conditions, most of which involve genetic causes. We describe the variable spectrum of findings and clinical impacts of exome sequencing (ES) in a cohort of 500 patients with rare diseases. In total, 164 primary findings were reported in 158 patients, representing an overall diagnostic yield of 31.6%. Most of the findings (61.6%) corresponded to autosomal dominant conditions, followed by autosomal recessive (25.6%) and X‐linked (12.8%) conditions. These patients harbored 195 variants, among which 43.6% are novel in the literature. The rate of molecular diagnosis was considerably higher for prenatal samples (67%; 4/6), younger children (44%; 24/55), consanguinity (50%; 3/6), gastrointestinal/liver disease (44%; 16/36) and syndromic/malformative conditions (41%; 72/175). For 15.6% of the cohort patients, we observed a direct potential for the redirection of care with targeted therapy, tumor screening, medication adjustment and monitoring for disease‐specific complications. Secondary findings were reported in 37 patients (7.4%). Based on cost‐effectiveness studies in the literature, we speculate that the reports of secondary findings may influence an increase of 123.2 years in the life expectancy for our cohort, or 0.246 years/cohort patient. ES is a powerful method to identify the molecular bases of monogenic disorders and redirect clinical care.