A Truncating Mutation of TRAPPC9 Is Associated with Autosomal-Recessive Intellectual Disability and Postnatal Microcephaly

作者：Mochida Ganeshwaran H; Mahajnah Muhammad; Hill Anthony D; Basel Vanagaite Lina; Gleason Danielle; Hill R Sean; Bodell Adria; Crosier Moira; Straus**erg Rachel; Walsh Christopher A^*

来源：American Journal of Human Genetics, 2009, 85(6): 897-902.

DOI：10.1016/j.ajhg.2009.10.027

Although autosomal genes are increasingly recognized as important causes of intellectual disability, very few of them are known. We identified a genetic locus for autosomal-recessive nonsyndromic intellectual disability associated with variable postnatal microcephaly through homozygosity mapping of a consanguineous Israeli Arab family. Sequence analysis of genes in the candidate interval identified a nonsense nucleotide change in the gene that encodes TRAPPC9 (trafficking protein particle complex 9, also known as NIBP), which has been implicated in NF-kappa B activation and possibly in intracellular protein trafficking. TRAPPC9 is highly expressed in the postmitotic neurons of the cerebral cortex, and MRI analysis of affected patients shows defects in axonal connectivity. This suggests essential roles of TRAPPC9 in human brain development, possibly through its effect on NF-kappa B activation and protein trafficking in the postmitotic neurons of the cerebral cortex.

• 出版日期2009-12-11