Molecular diagnosis of somatic overgrowth conditions: A single‐center experience

• DOI: 10.1002/mgg3.536
• Publication Date: 2019-02-14T05:13:44Z
• Authors: Emilie Lalonde; Jessica Ebrahimzadeh; Keith Rafferty; Jennifer Richards...; Richard Grant; Erik Toorens; Jennifer Marie Ro...; Erica Schindewolf; Tapan Ganguly; Jennifer M. Kalish; Matthew A. Deardorff; Arupa Ganguly
• Keywords: 0303 health sciences; Class I Phosphatidylinositol 3-Kinases; Vascular Malformations; Original Articles; Sequence Analysis, DNA; Musculoskeletal Abnormalities; Proteus Syndrome; 03 medical and health sciences; Sturge-Weber Syndrome; Mutation; Humans; Genetic Testing; Lipoma; Nevus

Abstract Background Somatic overgrowth conditions, including Proteus syndrome, Sturge–Weber and PIK3CA ‐related spectrum, are caused by post‐zygotic pathogenic variants, result in segmental mosaicism, give rise to neural, cutaneous and/or lipomatous overgrowth. These variants occur growth‐promoting pathways leading cellular proliferation expansion of tissues that arise from the affected lineage. Methods We report on 80 serial patients evaluated for somatic conditions a diagnostic laboratory setting, three prenatal patients. In total, 166 these were subjected targeted sequencing an 8‐gene panel capturing 10.2 kb sequence containing known associated with conditions. Deep next‐generation was performed IonTorrent PGM platform at average depth typically >5,000×. Results Likely or identified 36 individuals unknown significance four. The overall molecular yield 45% but highly influenced both submitted tissue type phenotype. two had cultured amniocytes third patient, variant only present post‐natal tissues. Finally, expanding test include full gene contrast likely 3 7 tested negative original panel. Conclusion Next‐generation has enabled sensitive detection However, as allele frequency varies within individual, submission tissue(s) greatly increases chances diagnosis.