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Mutations in the exocyst component EXOC2 (Sec5) cause severe defects in human brain development

ABSTRACT: The exocyst is an octameric protein complex and an essential component of the membrane transport machinery required for tethering vesicles at the plasma membrane prior to fusion. Here we report on pathogenic variants in one of the exocyst subunits, EXOC2 (Sec5), in unrelated families. Analysis of patient’s fibroblasts revealed reduced protein levels in Family 1, impaired secretory vesicle fusion with the plasma membrane and defective bulk exocytosis. Based on genetic and functional genomics findings, we suggest that the EXOC2 variants we have identified are the cause of the neurological disorder in these patients.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Skin, Fibroblast

SUBMITTER: David Stroud

LAB HEAD: David Arthur Stroud

PROVIDER: PXD017107 | Pride | 2020-06-29

REPOSITORIES: Pride

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Mutations in the exocyst component EXOC2 cause severe defects in human brain development.

Van Bergen Nicole J NJ Ahmed Syed Mukhtar SM Collins Felicity F Cowley Mark M Vetro Annalisa A Dale Russell C RC Hock Daniella H DH de Caestecker Christian C Menezes Minal M Massey Sean S Ho Gladys G Pisano Tiziana T Glover Seana S Gusman Jovanka J Stroud David A DA Dinger Marcel M Guerrini Renzo R Macara Ian G IG Christodoulou John J

The Journal of experimental medicine 20201001 10

The exocyst, an octameric protein complex, is an essential component of the membrane transport machinery required for tethering and fusion of vesicles at the plasma membrane. We report pathogenic variants in an exocyst subunit, EXOC2 (Sec5). Affected individuals have severe developmental delay, dysmorphism, and brain abnormalities; variability associated with epilepsy; and poor motor skills. Family 1 had two offspring with a homozygous truncating variant in EXOC2 that leads to nonsense-mediated ...[more]

PMID: 32639540

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