Uncovering the Genetic Mechanism Responsible for Microcephaly–Capillary Malformation Syndrome

Mutations in STAMBP that affect RAS and PI3K signaling are linked to microcephaly and capillary malformation in this developmental disorder.

Microcephaly–capillary malformation (MIC-CAP) syndrome is characterized by multiple cutaneous capillary malformations, epilepsy, cortical atrophy, microcephaly, and growth retardation. The capillary malformations are visible at birth (size range, 2–20 mm) and are associated with visceral angiomas.

The genetic basis for this disorder has been discovered by McDonell and colleagues. Using whole-exome sequencing of five affected individuals, they identified recessive inactivating mutations in the STAMBP gene that result in removal of ubiquitin from proteins. Ubiquitin is a small protein tag that targets the proteins to which it is attached for endosomal sorting (important for signal transduction and autophagy) or regulated destruction. Cells lac…

Reviewing Author

Kenneth Y. Tsai, MD, PhD

Disclosures

Grant / Research support American Association for Cancer Research – Landon Foundation; National Institutes of Health/National Cancer Institute; Cancer Prevention Research Institute of Texas

Editorial BoardsJournal of the American Academy of Dermatology

Kenneth Y. Tsai, MD, PhD

Disclosures

Grant / Research support American Association for Cancer Research – Landon Foundation; National Institutes of Health/National Cancer Institute; Cancer Prevention Research Institute of Texas

Editorial BoardsJournal of the American Academy of Dermatology