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

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

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
JournalAmerican Journal of Human Genetics
DOIs
StateAccepted/In press - Sep 22 2015

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ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

You, J., Sobreira, N., Gable, D. L., Jurgens, J., Grange, D. K., Belnap, N., Siniard, A., Szelinger, S., Schrauwen, I., Richholt, R. F., Vallee, S. E., Dinulos, M. B. P., Valle, D., Armanios, M., & Hoover Fong, J. E. (Accepted/In press). A Syndromic Intellectual Disability Disorder Caused by Variants in TELO2, a Gene Encoding a Component of the TTT Complex. American Journal of Human Genetics. https://doi.org/10.1016/j.ajhg.2016.03.014