title: Somatic mosaicism of the PIK3CA gene identified in a Hungarian girl with macrodactyly and syndactyly.
abstract: Isolated macrodactyly (OMIM 155500) belongs to a heterogeneous group of overgrowth syndromes. It is a congenital anomaly resulting in enlargement of all tissues localized to the terminal portions of a limb and caused by somatic mutations in the phosphatidylinositol 3-kinase catalytic alpha (PIK3CA, OMIM 171834) gene. Here we report a Hungarian girl with macrodactyly and syndactyly. Genetic screening at hotspots in the PIK3CA gene identified a mosaic mutation (c.1624G > A, p.Glu542Lys) in the affected tissue, but not in the peripheral blood. To date, this somatic mutation has been reported in eight patients affected by different forms of segmental overgrowth syndromes. Detailed analysis of the Hungarian child and previously reported cases suggests high phenotypic diversity associated with the p.Glu542Lys somatic mutation. The identification of the mutation provides a novel therapeutic modality for the affected patients: those who carry somatic mutations in the PIK3CA gene are potential recipients of a novel "repurposing" approach of rapamycin treatment.
authors: Department of Medical Genetics, University of Szeged, Szeged, Hungary.
authors: Kornélia
authors: K
authors: Tripolszki
authors: Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke's Hospital Cambridge, Cambridge, UK.
authors: Rachel
authors: R
authors: Knox
authors: Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke's Hospital Cambridge, Cambridge, UK.
authors: Victoria
authors: V
authors: Parker
authors: Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke's Hospital Cambridge, Cambridge, UK.
authors: Robert
authors: R
authors: Semple
authors: MTA-SZTE Dermatological Research Group, University of Szeged, Szeged, Hungary.
authors: Katalin
authors: K
authors: Farkas
authors: Department of Medical Genetics, University of Szeged, Szeged, Hungary.
authors: Adrien
authors: A
authors: Sulák
authors: Department of Medical Genetics, University of Szeged, Szeged, Hungary.
authors: Emese
authors: E
authors: Horváth
authors: Department of Medical Genetics, University of Szeged, Szeged, Hungary; MTA-SZTE Dermatological Research Group, University of Szeged, Szeged, Hungary.
authors: Márta
authors: M
authors: Széll
authors: Department of Medical Genetics, University of Szeged, Szeged, Hungary; MTA-SZTE Dermatological Research Group, University of Szeged, Szeged, Hungary. Electronic address: nikoletta.nagy@gmail.com.
authors: Nikoletta
authors: N
authors: Nagy
mesh_terms: D002675:Child, Preschool; D058534:Class I Phosphatidylinositol 3-Kinases; D005260:Female; D005385:Fingers / Q000002:abnormalities* / Q000473:pathology; D006801:Humans; D006814:Hungary; D017880:Limb Deformities, Congenital / Q000235:genetics* / Q000473:pathology; D009030:Mosaicism; D009154:Mutation; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D013576:Syndactyly / Q000235:genetics* / Q000473:pathology
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human
keywords: Macrodactyly and syndactyly; Overgrowth syndromes; PIK3CA gene; Phenotypic diversity; Somatic mutation