ClinVar

CLOVE Syndrome

In a 14-year-old girl and an unrelated 1-year-old boy with CLOVE syndrome (612918), Kurek et al. (2012) identified somatic mosaicism for a 1624G-A transition in the PIK3CA gene, resulting in a glu542-to-lys (E542K) substitution that was present in affected tissues from multiple embryonic lineages with a mutant allele frequency ranging from 6 to 13%.

CLAPO Syndrome

In tissue from a lower lip capillary malformation (CM) from a 2-year-old female patient (P10) with CLAPO syndrome (613089), Rodriguez-Laguna et al. (2018) identified a c.1624G-A transition (c.1624G-A, NM_006218.2) in the PIK3CA gene that resulted in a glu542-to-lys (E542K) mutation in the helical domain. The mutation was present at an allele frequency of 10% by deep sequencing, was present in 999 samples from the Catalogue of Somatic Mutations in Cancer (COSMIC) database, and had been previously reported in 44 patients with vascular overgrowth disorders. Functional studies were not performed.

Cerebral Cavernous Malformations 4

In samples of cerebral cavernous malformations-4 (CCM4; 619538) from 16 unrelated patients with sporadic occurrence of the disease, Peyre et al. (2021) identified a somatic E542K mutation in the PIK3CA gene. The mutation was found by targeted DNA sequencing. PIK3CA-mutant CCMs showed increased phosphorylation of myosin light chain and activation of the PI3K-AKT-mTOR pathway, consistent with an activating mutation.

Hemifacial Myohyperplasia

In 2 patients (patients 3 and 4) with hemifacial myohyperplasia (HFMH; 606773), Bayard et al. (2023) identified mosaicism for the E542K mutation in the PIK3CA gene. Bayard et al. (2023) performed genotyping on muscle biopsies from affected regions and found a mutation burden of 12% in patient 3 and 21% in patient 4.