Authors
Laura M McDonell, Ghayda M Mirzaa, Diana Alcantara, Jeremy Schwartzentruber, Melissa T Carter, Leo J Lee, Carol L Clericuzio, John M Graham Jr, Deborah J Morris-Rosendahl, Tilman Polster, Gyula Acsadi, Sharron Townshend, Simon Williams, Anne Halbert, Bertrand Isidor, Albert David, Christopher D Smyser, Alex R Paciorkowski, Marcia Willing, John Woulfe, Soma Das, Chandree L Beaulieu, Janet Marcadier, FORGE Canada Consortium Boycott K Friedman J Michaud J Bernier F Brudno M Fernandez B Knoppers B Samuels M Scherer S, Michael T Geraghty, Brendan J Frey, Jacek Majewski, Dennis E Bulman, William B Dobyns, Mark O'Driscoll, Kym M Boycott
Publication date
2013/5
Journal
Nature genetics
Volume
45
Issue
5
Pages
556-562
Publisher
Nature Publishing Group US
Description
Microcephaly–capillary malformation (MIC-CAP) syndrome is characterized by severe microcephaly with progressive cortical atrophy, intractable epilepsy, profound developmental delay and multiple small capillary malformations on the skin. We used whole-exome sequencing of five patients with MIC-CAP syndrome and identified recessive mutations in STAMBP, a gene encoding the deubiquitinating (DUB) isopeptidase STAMBP (STAM-binding protein, also known as AMSH, associated molecule with the SH3 domain of STAM) that has a key role in cell surface receptor–mediated endocytosis and sorting. Patient cell lines showed reduced STAMBP expression associated with accumulation of ubiquitin-conjugated protein aggregates, elevated apoptosis and insensitive activation of the RAS-MAPK and PI3K-AKT-mTOR pathways. The latter cellular phenotype is notable considering the established connection …
Scholar articles
LM McDonell, GM Mirzaa, D Alcantara… - Nature genetics, 2013