A Syndromic Intellectual Disability Disorder Caused by Variants in TELO2, a Gene Encoding a Component of the TTT Complex

作者：You Jing; Sobreira Nara L; Gable Dustin L; Jurgens Julie; Grange Dorothy K; Belnap Newell; Siniard Ashley; Szelinger Szabolcs; Schrauwen Isabelle; Richholt Ryan F; Vallee Stephanie E; Dinulos Mary Beth P; Valle David^*; Armanios Mary; Hoover Fong Julie

来源：American Journal of Human Genetics, 2016, 98(5): 909-918.

DOI：10.1016/j.ajhg.2016.03.014

The proteins encoded by TELO2, TTI1, and TTI2 interact to form the TTT complex, a co-chaperone for maturation of the phosphatidylinositol 3-kinase-related protein kinases (PIKKs). Here we report six affected individuals from four families with intellectual disability (ID) and neurological and other congenital abnormalities associated with compound heterozygous variants in TELO2. Although their fibroblasts showed reduced steady-state levels of TELO2 and the other components of the TTT complex, PIKK functions were normal in cellular assays. Our results suggest that these TELO2 missense variants result in loss of function, perturb TTT complex stability, and cause an autosomal-recessive syndromic form of ID.

• 出版日期2016-5-5