Severe neurocognitive and growth disorders due to variation in THOC2, an essential component of nuclear mRNA export machinery.

ABSTRACT: Highly conserved TREX-mediated mRNA export is emerging as a key pathway in neuronal development and differentiation. TREX subunit variants cause neurodevelopmental disorders (NDDs) by interfering with mRNA export from the cell nucleus to the cytoplasm. Previously we implicated four missense variants in the X-linked THOC2 gene in intellectual disability (ID). We now report an additional six affected individuals from five unrelated families with two de novo and three maternally inherited pathogenic or likely pathogenic variants in THOC2 extending the genotypic and phenotypic spectrum. These comprise three rare missense THOC2 variants that affect evolutionarily conserved amino acid residues and reduce protein stability and two with canonical splice-site THOC2 variants that result in C-termina

SUBMITTER: Kumar R 

PROVIDER: S-EPMC6481655 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature