Phenotypic and molecular characterization of five patients with PIK3CA-related overgrowth spectrum (PROS)


Ili E. G. , Tasdelen E., Durmaz C. D. , ALTINER Ş., TUNCALI T., Martinez-Glez V., ...More

AMERICAN JOURNAL OF MEDICAL GENETICS PART A, 2022 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Publication Date: 2022
  • Doi Number: 10.1002/ajmg.a.62709
  • Title of Journal : AMERICAN JOURNAL OF MEDICAL GENETICS PART A
  • Keywords: overgrowth spectrum, PIK3CA, PROS, somatic mosaicism, ACTIVATING MUTATIONS, PIK3CA MUTATIONS, DIFFERENTIAL-DIAGNOSIS, SOMATIC MUTATIONS, PROTEUS-SYNDROME, NATURAL-HISTORY, CUTIS MARMORATA, EPIDERMAL-NEVI, PATHWAY, DISORDERS

Abstract

Somatic and germline PI3K-AKT-mTOR pathway pathogenic variants are involved in several segmental overgrowth phenotypes such as the PIK3CA-related overgrowth spectrum (PROS), Proteus syndrome, and PTEN hamartoma tumor syndrome. In this study, we describe five patients with PROS. We identified by high-throughput sequencing four different somatic PIK3CA pathogenic variants in five individuals. The Glu726Lys variant, which was previously reported in megalencephaly-capillary malformation-polymicrogyria (MCAP) syndrome, was identified in two patients with unclassified PROS. The Cys420Arg substitution, which was previously reported in CLOVES, was found in a patient with fibroadipose hyperplasia. Additionally, relatively rare pathogenic variants, His1047Tyr and Tyr1021Cys, were detected in two patients with MCAP. Therefore, we suggest performing deep sequencing of PIK3CA in all patients with suspected PROS, instead of targeted polymerase chain reaction for hotspot pathogenic variants.