Dominant LMAN2L mutation causes intellectual disability with remitting epilepsy.

Abstract

Mis-secreted glycoproteins (LGI1, reelin) are emerging causes of epilepsy. LMAN2L belongs to a glycoprotein secretion chaperone family. One recessive LMAN2L missense mutation predicted to impair the chaperone's interaction with glycoproteins was reported in a family with intellectual disability (ID) and remitting epilepsy. We describe four members of a family with autosomal dominant inheritance of a similar phenotype. We show that they segregate a NM_001142292.1:c.1073delT mutation that eliminates LMAN2L's endoplasmic reticulum retention signal and mislocalizes the protein from that compartment to the plasma membrane. LMAN2L mislocalization, like impaired glycoprotein interaction, disturbs brain development, including generation of developmentally restricted epilepsy.

• Authors: Reem A Alkhater, Peixiang Wang, Alessandra Ruggieri, Lori Israelian, Susan Walker, Stephen W Scherer, Mary Lou Smith, Berge A Minassian
• Journal: Annals of clinical and translational neurology (Ann Clin Transl Neurol) Vol. 6 Issue 4 Pg. 807-811 (Apr 2019) ISSN: 2328-9503 [Print] United States
• PMID: 31020005 (Publication Type: Case Reports, Journal Article)

Chemical References

• LMAN2L protein, human
• Lectins
• Membrane Transport Proteins
• Reelin Protein
• RELN protein, human

Topics

• Child
• Child, Preschool
• Epilepsy (diagnosis, genetics)
• Humans
• Intellectual Disability (diagnosis, genetics)
• Lectins (genetics)
• Male
• Membrane Transport Proteins (genetics)
• Middle Aged
• Mutation (genetics)
• Pedigree
• Phenotype
• Reelin Protein