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Multiplex targeted high‐throughput sequencing in a series of 352 patients with congenital limb malformations
Author(s) -
Jourdain AnneSophie,
Petit Florence,
Odou MarieFrançoise,
Balduyck Malika,
Brunelle Perrine,
Dufour William,
Boussion Simon,
BrischouxBoucher Elise,
Colson Cindy,
Dieux Anne,
Gérard Marion,
Ghoumid Jamal,
Giuliano Fabienne,
Goldenberg Alice,
Khau Van Kien Philippe,
Lehalle Daphné,
Morin Gilles,
Moutton Sébastien,
Smol Thomas,
Vanlerberghe Clémence,
ManouvrierHanu Sylvie,
Escande Fabienne
Publication year - 2020
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.23912
Subject(s) - multiplex , dna sequencing , copy number variation , phenotype , computational biology , medicine , congenital malformations , triage , clinical practice , gene , bioinformatics , genetics , biology , genome , pregnancy , emergency medicine , family medicine
Congenital limb malformations (CLM) comprise many conditions affecting limbs and more than 150 associated genes have been reported. Due to this large heterogeneity, a high proportion of patients remains without a molecular diagnosis. In the last two decades, advances in high throughput sequencing have allowed new methodological strategies in clinical practice. Herein, we report the screening of 52 genes/regulatory sequences by multiplex high‐throughput targeted sequencing, in a series of 352 patients affected with various CLM, over a 3‐year period of time. Patients underwent a clinical triage by expert geneticists in CLM. A definitive diagnosis was achieved in 35.2% of patients, the yield varying considerably, depending on the phenotype. We identified 112 single nucleotide variants and 26 copy‐number variations, of which 52 are novel pathogenic or likely pathogenic variants. In 6% of patients, variants of uncertain significance have been found in good candidate genes. We showed that multiplex targeted high‐throughput sequencing works as an efficient and cost‐effective tool in clinical practice for molecular diagnosis of congenital limb malformations. Careful clinical evaluation of patients may maximize the yield of CLM panel testing.