A recurrent variant in two patients with EMP2-nEDD.

We identify a recurrent de novo heterozygous variant (c.11T>C, p.Leu4Pro) in EMP2 as a cause of EMP2-nEDD in two sporadic patients. Functional studies revealed that the variant exhibited significantly reduced localization at the plasma membrane, disrupting lipid raft integrity and triggering ligand-independent EGFR activation and internalization. Consequently, treatment with the EGFR inhibitor erlotinib led to significant clinical improvement in one patient after one month.