Delineation of the phenotypes and genotypes of PIK3CA-related overgrowth spectrum in East asians.
PIK3CA variant
PIK3CA-related overgrowth spectrum
East Asian
Genotype
PROS
Phenotype
Journal
Molecular genetics and genomics : MGG
ISSN: 1617-4623
Titre abrégé: Mol Genet Genomics
Pays: Germany
ID NLM: 101093320
Informations de publication
Date de publication:
09 Jul 2024
09 Jul 2024
Historique:
received:
26
01
2024
accepted:
20
06
2024
medline:
9
7
2024
pubmed:
9
7
2024
entrez:
9
7
2024
Statut:
epublish
Résumé
PIK3CA-related overgrowth spectrum (PROS) is an umbrella term to describe a diverse range of developmental disorders. Research to date has predominantly emerged from Europe and North America, resulting in a notable scarcity of studies focusing on East Asian populations. Currently, the prevalence and distribution of PIK3CA variants across various genetic loci and their correlation with distinct phenotypes in East Asian populations remain unclear. This study aims to elucidate the phenotype-genotype correlations of PROS in East Asian populations. We presented the phenotypes and genotypes of 82 Chinese patients. Among our cohort, 67 individuals carried PIK3CA variants, including missense, frameshift, and splice variants. Six patients presented with both PIK3CA and an additional variant. Seven PIK3CA-negative patients exhibited overlapping PROS manifestations with variants in GNAQ, AKT1, PTEN, MAP3K3, GNA11, or KRAS. An integrative review of the literature pertaining to East Asian populations revealed that specific variants are uniquely associated with certain PROS phenotypes. Some rare variants were exclusively identified in cases of megalencephaly and diffuse capillary malformation with overgrowth. Non-hotspot variants with undefined oncogenicity were more common in CNS phenotypes. Diseases with vascular malformation were more likely to have variants in the helical domain, whereas phenotypes involving adipose/muscle overgrowth without vascular abnormalities predominantly presented variants in the C2 domain. Our findings underscore the unique phenotype-genotype patterns within the East Asian PROS population, highlighting the necessity for an expanded cohort to further elucidate these correlations. Such endeavors would significantly facilitate the development of PI3Kα selective inhibitors tailored for the East Asian population in the future.
Identifiants
pubmed: 38980418
doi: 10.1007/s00438-024-02159-w
pii: 10.1007/s00438-024-02159-w
doi:
Substances chimiques
Class I Phosphatidylinositol 3-Kinases
EC 2.7.1.137
PIK3CA protein, human
EC 2.7.1.137
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
66Subventions
Organisme : Major and Key Cultivation Projects of Ninth People's Hospital affiliated to Shanghai Jiao Tong University School of Medicine
ID : JYZP005
Organisme : Treatment and mechanism of PI3K/mTOR dual-target inhibitor (WX390) on PIK3CA-related overgrowth spectrum (PROS)
ID : JYWO22075
Organisme : Shanghai Sailing Program
ID : 22YF1421900
Organisme : Rare Disease Registration Platform of Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine
ID : JYHJB02
Informations de copyright
© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
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