%0 Journal Article
%T Biallelic Loss of Function Variants in SENP7 Cause Immunodeficiency with Neurologic and Muscular Phenotypes.
%A Kobayashi ES
%A Lotan NS
%A Schejter YD
%A Makowski C
%A Kraus V
%A Ramchandar N
%A Meiner V
%A Thiffault I
%A Farrow E
%A Cakici J
%A Kingsmore S
%A Wagner M
%A Rieber N
%A Bainbridge M
%J J Pediatr
%V 274
%N 0
%D 2024 Jul 5
%M 38972567
%F 6.314
%R 10.1016/j.jpeds.2024.114180
%X To evaluate a novel candidate disease gene, we engaged international collaborators and identified rare, biallelic, specifically homozygous, loss of function variants in SENP7 in 4 children from 3 unrelated families presenting with neurodevelopmental abnormalities, dysmorphism, and immunodeficiency. Their clinical presentations were characterized by hypogammaglobulinemia, intermittent neutropenia, and ultimately death in infancy for all 4 patients. SENP7 is a sentrin-specific protease involved in posttranslational modification of proteins essential for cell regulation, via a process referred to as deSUMOylation. We propose that deficiency of deSUMOylation may represent a novel mechanism of primary immunodeficiency.