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Early activating somatic PIK3CA mutations promote ectopic muscle development and upper limb overgrowth.
Frisk, Sofia; Taylan, Fulya; Blaszczyk, Izabela; Nennesmo, Inger; Annerén, Göran; Herm, Bettina; Stattin, Eva-Lena; Zachariadis, Vasilios; Lindstrand, Anna; Tesi, Bianca; Laurell, Tobias; Nordgren, Ann.
Afiliación
  • Frisk S; Department of Molecular Medicine and Surgery, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
  • Taylan F; Department of Clinical Genetics, Karolinska University Laboratory, Karolinska University Hospital, Stockholm, Sweden.
  • Blaszczyk I; Department of Molecular Medicine and Surgery, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
  • Nennesmo I; Department of Surgical and Perioperative Sciences, Hand and Plastic Surgery, Umeå University Hospital, Umeå, Sweden.
  • Annerén G; Department of Pathology, Karolinska University Hospital, Stockholm, Sweden.
  • Herm B; Science for Life Laboratory, Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
  • Stattin EL; Child and Adolescent Habilitation Centre, Östersunds Hospital, Östersund, Sweden.
  • Zachariadis V; Science for Life Laboratory, Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
  • Lindstrand A; Department of Molecular Medicine and Surgery, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
  • Tesi B; Department of Molecular Medicine and Surgery, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
  • Laurell T; Department of Clinical Genetics, Karolinska University Laboratory, Karolinska University Hospital, Stockholm, Sweden.
  • Nordgren A; Department of Molecular Medicine and Surgery, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
Clin Genet ; 96(2): 118-125, 2019 08.
Article en En | MEDLINE | ID: mdl-30919936
PIK3CA-related overgrowth spectrum is a group of rare genetic disorders with asymmetric overgrowth caused by somatic mosaic PIK3CA mutations. Here, we report clinical data and molecular findings from two patients with congenital muscular upper limb overgrowth and aberrant anatomy. During debulking surgery, numerous ectopic muscles were found in the upper limbs of the patients. DNA sequencing, followed by digital polymerase chain reaction, was performed on DNA extracted from biopsies from hypertrophic ectopic muscles and identified the somatic mosaic PIK3CA hotspot mutations c.3140A > G, p.(His1047Arg) and c.1624G > A, p.(Glu542Lys) in a male (patient 1) and a female (patient 2) patient, respectively. Patient 1 had four ectopic muscles and unilateral isolated muscular overgrowth while patient 2 had 13 ectopic muscles and bilateral isolated muscular overgrowth of both upper limbs, indicating that her mutation occurred at early pre-somitic mesoderm state. The finding of PIK3CA mutations in ectopic muscles highlights the importance of PIK3CA in cell fate in early human embryonic development. Moreover, our findings provide evidence that the disease phenotype depends on the timing of PIK3CA mutagenesis during embryogenesis and confirm the diagnostic entity PIK3CA-related muscular overgrowth with ectopic accessory muscles.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Músculo Esquelético / Desarrollo de Músculos / Extremidad Superior / Fosfatidilinositol 3-Quinasa Clase I / Expresión Génica Ectópica / Mutación Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Clin Genet Año: 2019 Tipo del documento: Article País de afiliación: Suecia Pais de publicación: Dinamarca
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Músculo Esquelético / Desarrollo de Músculos / Extremidad Superior / Fosfatidilinositol 3-Quinasa Clase I / Expresión Génica Ectópica / Mutación Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Clin Genet Año: 2019 Tipo del documento: Article País de afiliación: Suecia Pais de publicación: Dinamarca