Molecular diagnosis of PIK3CA-related overgrowth spectrum (PROS) in 162 patients and recommendations for genetic testing. - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Genetics in Medicine Année : 2017

Molecular diagnosis of PIK3CA-related overgrowth spectrum (PROS) in 162 patients and recommendations for genetic testing.

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Jeanne Amiel
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Sébastien Barbarot
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Olivia Boccara
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Christine Chiaverini
Patrick Edery
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Damien Haye
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Ludovic Martin
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Annabel Maruani
Juliette Mazereeuw-Hautier
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  • PersonId : 1110200
Caroline Michot
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Florence Petit
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Alain Verloes
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Sandra Whalen
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Résumé

Postzygotic activating mutations of PIK3CA cause a wide range of mosaic disorders collectively referred to as PIK3CA-related overgrowth spectrum (PROS). We describe the diagnostic yield and characteristics of PIK3CA sequencing in PROS. METHODS: We performed ultradeep next-generation sequencing (NGS) of PIK3CA in various tissues from 162 patients referred to our clinical laboratory and assessed diagnostic yield by phenotype and tissue tested. RESULTS: We identified disease-causing mutations in 66.7% (108/162) of patients, with mutant allele levels as low as 1%. The diagnostic rate was higher (74%) in syndromic than in isolated cases (35.5%; P = 9.03 × 10-5). We identified 40 different mutations and found strong oncogenic mutations more frequently in patients without brain overgrowth (50.6%) than in those with brain overgrowth (15.2%; P = 0.00055). Mutant allele levels were higher in skin and overgrown tissues than in blood and buccal samples (P = 3.9 × 10-25), regardless of the phenotype. CONCLUSION: Our data demonstrate the value of ultradeep NGS for molecular diagnosis of PROS, highlight its substantial allelic heterogeneity, and confirm that optimal diagnosis requires fresh skin or surgical samples from affected regions. Our findings may be of value in guiding future recommendations for genetic testing in PROS and other mosaic conditions

Dates et versions

hal-01560452 , version 1 (11-07-2017)

Identifiants

Citer

Paul Kuentz, Judith Saint-Onge, Yannis Duffourd, Jean-Benoît Courcet, Virginie Carmignac, et al.. Molecular diagnosis of PIK3CA-related overgrowth spectrum (PROS) in 162 patients and recommendations for genetic testing.. Genetics in Medicine, 2017, 19 (9), pp.989-997. ⟨10.1038/gim.2016.220⟩. ⟨hal-01560452⟩
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