Lara Rodriguez-Laguna1, Kristina Ibañez2, Gema Gordo1,3, Sixto Garcia-Minaur3,4, Fernando Santos-Simarro3,4, Noelia Agra1, Elena Vallespín3,5, Victoria E Fernández-Montaño5, Rubén Martín-Arenas5, Ángela Del Pozo2, Héctor González-Pecellín5, Rocío Mena3,5, Inmaculada Rueda-Arenas5, María V Gomez5, Cristina Villaverde3,6, Ana Bustamante3,6, Carmen Ayuso3,6, Víctor L Ruiz-Perez3,7, Julián Nevado3,5, Pablo Lapunzina3,4, Juan C Lopez-Gutierrez8, Victor Martinez-Glez9,10. 1. Vascular Malformations Section, Institute of Medical and Molecular Genetics, INGEMM-IdiPAZ, Hospital Universitario La Paz, Madrid, Spain. 2. Bioinformatics Section, Institute of Medical and Molecular Genetics, INGEMM-IdiPAZ, Hospital Universitario La Paz, Madrid, Spain. 3. CIBERER, Centro de Investigación Biomédica en Red de Enfermedades Raras, ISCIII, Madrid, Spain. 4. Clinical Genetics Section, Institute of Medical and Molecular Genetics, INGEMM-IdiPAZ, Hospital Universitario La Paz, Madrid, Spain. 5. Structural and Functional Genomics Section, Institute of Medical and Molecular Genetics, INGEMM-IdiPAZ, Hospital Universitario La Paz, Madrid, Spain. 6. Department of Genetics, IIS-Fundación Jiménez Díaz UAM, Madrid, Spain. 7. Instituto de Investigaciones Biomédicas "Alberto Sols," CSIC-UAM, Madrid, Spain. 8. Vascular Anomalies Center, Plastic Surgery, Hospital Universitario La Paz, Madrid, Spain. queminfantil.hulp@salud.madrid.org. 9. Vascular Malformations Section, Institute of Medical and Molecular Genetics, INGEMM-IdiPAZ, Hospital Universitario La Paz, Madrid, Spain. vmartineglez@salud.madrid.org. 10. CIBERER, Centro de Investigación Biomédica en Red de Enfermedades Raras, ISCIII, Madrid, Spain. vmartineglez@salud.madrid.org.
Abstract
PURPOSE: CLAPO syndrome is a rare vascular disorder characterized by capillary malformation of the lower lip, lymphatic malformation predominant on the face and neck, asymmetry, and partial/generalized overgrowth. Here we tested the hypothesis that, although the genetic cause is not known, the tissue distribution of the clinical manifestations in CLAPO seems to follow a pattern of somatic mosaicism. METHODS: We clinically evaluated a cohort of 13 patients with CLAPO and screened 20 DNA blood/tissue samples from 9 patients using high-throughput, deep sequencing. RESULTS: We identified five activating mutations in the PIK3CA gene in affected tissues from 6 of the 9 patients studied; one of the variants (NM_006218.2:c.248T>C; p.Phe83Ser) has not been previously described in developmental disorders. CONCLUSION: We describe for the first time the presence of somatic activating PIK3CA mutations in patients with CLAPO. We also report an update of the phenotype and natural history of the syndrome.
PURPOSE: CLAPO syndrome is a rare vascular disorder characterized by capillary malformation of the lower lip, lymphatic malformation predominant on the face and neck, asymmetry, and partial/generalized overgrowth. Here we tested the hypothesis that, although the genetic cause is not known, the tissue distribution of the clinical manifestations in CLAPO seems to follow a pattern of somatic mosaicism. METHODS: We clinically evaluated a cohort of 13 patients with CLAPO and screened 20 DNA blood/tissue samples from 9 patients using high-throughput, deep sequencing. RESULTS: We identified five activating mutations in the PIK3CA gene in affected tissues from 6 of the 9 patients studied; one of the variants (NM_006218.2:c.248T>C; p.Phe83Ser) has not been previously described in developmental disorders. CONCLUSION: We describe for the first time the presence of somatic activating PIK3CA mutations in patients with CLAPO. We also report an update of the phenotype and natural history of the syndrome.
Authors: Sofia Douzgou; Myfanwy Rawson; Eulalia Baselga; Moise Danielpour; Laurence Faivre; Alon Kashanian; Kim M Keppler-Noreuil; Paul Kuentz; Grazia M S Mancini; Marie-Cecile Maniere; Victor Martinez-Glez; Victoria E Parker; Robert K Semple; Siddharth Srivastava; Pierre Vabres; Marie-Claire Y De Wit; John M Graham; Jill Clayton-Smith; Ghayda M Mirzaa; Leslie G Biesecker Journal: Clin Genet Date: 2021-07-16 Impact factor: 4.296