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

Jing You; Nara L. 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 Hoover-Fong

doi:10.1016/j.ajhg.2016.03.014

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

Jing You, Nara L. 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 Hoover-Fong

Research output: Contribution to journal › Article › peer-review

28 Scopus citations

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 language	English
Pages (from-to)	909-918
Number of pages	10
Journal	American journal of human genetics
Volume	98
Issue number	5
DOIs	https://doi.org/10.1016/j.ajhg.2016.03.014
State	Published - May 5 2016

Access to Document

10.1016/j.ajhg.2016.03.014

Cite this

You, J., Sobreira, N. L., 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. (2016). A Syndromic Intellectual Disability Disorder Caused by Variants in TELO2, a Gene Encoding a Component of the TTT Complex. American journal of human genetics, 98(5), 909-918. https://doi.org/10.1016/j.ajhg.2016.03.014

@article{7eb78216e19c46c1a0d83b92190c9511,

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

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.",

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

year = "2016",

month = may,

day = "5",

doi = "10.1016/j.ajhg.2016.03.014",

language = "English",

volume = "98",

pages = "909--918",

journal = "American journal of human genetics",

issn = "0002-9297",

number = "5",

}

You, J, Sobreira, NL, Gable, DL, Jurgens, J, Grange, DK, Belnap, N, Siniard, A, Szelinger, S, Schrauwen, I, Richholt, RF, Vallee, SE, Dinulos, MBP, Valle, D, Armanios, M & Hoover-Fong, J 2016, 'A Syndromic Intellectual Disability Disorder Caused by Variants in TELO2, a Gene Encoding a Component of the TTT Complex', American journal of human genetics, vol. 98, no. 5, pp. 909-918. https://doi.org/10.1016/j.ajhg.2016.03.014

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

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.

UR - http://www.scopus.com/inward/record.url?scp=84964664169&partnerID=8YFLogxK

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 -

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

Abstract

Access to Document

Other files and links

Fingerprint

Cite this