CDDC88A variants cause malformations of cortical development and immune dysfunction
A new study published in The Journal of Clinical Investigation characterized biallelic loss-of-function variants in the SPNS1 gene, coding for a lysosomal transmembrane protein implicated in lysosomal phospholipid catabolism. The variants were found among 2 families, suffering from progressive muscle weakness with elevated creatinine and liver injury associated with elevation of liver transaminases. Various analyses showed a negative effect on lysosomal and cellular lipid homeostasis in both patient and knockout fibroblasts, reinforcing the pathogenic relevance of these variants and underlining the importance of considering the SPNS1 gene in the diagnosis of lysosomal storage disease.
- J Clin Invest. 2025 Jul 3;135(17):e193099