Daphne J Smits, Rachel Schot, Nathalie Krusy, Katja Wiegmann, Olaf Utermöhlen, Monique T Mulder, Sandra den Hoedt, Grace Yoon, Ashish R Deshwar, Christina Kresge, Beth Pletcher, Maura van Mook, Marta Serio Ferreira, Raymond A Poot, Johan A Slotman, Gert-Jan Kremers, Abeer Ahmad, Buthaina Albash, Laila Bastaki, Dana Marafi, Jordy Dekker, Tjakko J van Ham, Laurent Nguyen, Grazia M S Mancini
Biallelic loss of function (LoF) variants in SMPD4 cause a rare and severe neurodevelopmental disorder with progressive congenital microcephaly and early death. SMPD4 encodes a sphingomyelinase that hydrolyzes sphingomyelin into ceramide at neutral pH and can thereby affect membrane lipid homeostasis. SMPD4 localizes to the membranes of the endoplasmic reticulum and nuclear envelope (NE), and interacts with nuclear pore complexes (NPC). We refine the clinical phenotype of LoF SMPD4 variants by describing five individuals from three unrelated families with longitudinal data due to prolonged survival...
February 3, 2023: Brain