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Early activating somatic PIK3CA mutations promote ectopic muscle development and upper limb overgrowth
Karolinska Inst, Ctr Mol Med, Dept Mol Med & Surg, Stockholm, Sweden;Karolinska Univ Hosp, Karolinska Univ Lab, Dept Clin Genet, Stockholm, Sweden.
Karolinska Inst, Ctr Mol Med, Dept Mol Med & Surg, Stockholm, Sweden.ORCID iD: 0000-0002-2907-0235
Umea Univ Hosp, Dept Surg & Perioperat Sci, Hand & Plast Surg, Umea, Sweden.
Karolinska Univ Hosp, Dept Pathol, Stockholm, Sweden.
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2019 (English)In: Clinical Genetics, ISSN 0009-9163, E-ISSN 1399-0004, Vol. 96, no 2, p. 118-125Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
WILEY , 2019. Vol. 96, no 2, p. 118-125
Keywords [en]
accessory, cell fate, ectopic, muscle hypertrophy, muscular hypertrophy, PIK3CA, PROS
National Category
Clinical Laboratory Medicine
Identifiers
URN: urn:nbn:se:uu:diva-390499DOI: 10.1111/cge.13543ISI: 000474933200002PubMedID: 30919936OAI: oai:DiVA.org:uu-390499DiVA, id: diva2:1341983
Funder
Swedish Childhood Cancer FoundationSwedish Cancer SocietySwedish Research CouncilSwedish Research CouncilBerth von Kantzows foundationThe Swedish Brain FoundationStockholm County CouncilAvailable from: 2019-08-12 Created: 2019-08-12 Last updated: 2019-08-12Bibliographically approved

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Annerén, GöranStattin, Evalena

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