TY - JOUR
T1 - A Syndromic Intellectual Disability Disorder Caused by Variants in TELO2, a Gene Encoding a Component of the TTT Complex
AU - You, Jing
AU - Sobreira, Nara L.
AU - Gable, Dustin L.
AU - Jurgens, Julie
AU - Grange, Dorothy K.
AU - Belnap, Newell
AU - Siniard, Ashley
AU - Szelinger, Szabolcs
AU - Schrauwen, Isabelle
AU - Richholt, Ryan F.
AU - Vallee, Stephanie E.
AU - Dinulos, Mary Beth P.
AU - Valle, David
AU - Armanios, Mary
AU - Hoover-Fong, Julie
N1 - Funding Information:
We are grateful for the families who participated in this study. This work was supported by the NHGRI grant 1U54HG006542 to the Baylor-Hopkins Center for Mendelian Genomics (D.V.), RO1CA160433, and the Commonwealth Foundation (to M.A.). J.Y., D. Gable, and J.J. are trainees of the Predoctoral Training Program in Human Genetics at Johns Hopkins University and are supported by the NIH training grant T32GM07814.
Publisher Copyright:
© 2016 The American Society of Human Genetics All rights reserved.
PY - 2016/5/5
Y1 - 2016/5/5
N2 - 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.
AB - 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.
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U2 - 10.1016/j.ajhg.2016.03.014
DO - 10.1016/j.ajhg.2016.03.014
M3 - Article
C2 - 27132593
AN - SCOPUS:84964664169
SN - 0002-9297
VL - 98
SP - 909
EP - 918
JO - American journal of human genetics
JF - American journal of human genetics
IS - 5
ER -