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Clin Genet. 2019 Jul 9. doi: 10.1111/cge.13603. [Epub ahead of print]

Confirmation that variants in TTI2 are responsible for autosomal recessive intellectual disability.

Author information

1
Département de Biochimie et Génétique du CHU d'Angers, Angers, France.
2
Mitolab, UMR INSERM 1083 - CNRS 6015, Université d'Angers, Angers, France.
3
Carle Clinics, Urbana, Illinois, USA.
4
GeneDx, Gaithersburg, Maryland, USA.
5
Service d'Endocrinologie Pédiatrique, CHU d'Angers, Angers, France.

Abstract

TTI2 (MIM 614126) has been described as responsible for autosomal recessive intellectual disability (MRT39, MIM:615541) in only two inbred families. Here, we give an account of two individuals from two unrelated outbred families harbouring compound heterozygous TTI2 pathogenic variants. Together with severe intellectual disability, progressive microcephaly, scoliosis and sleeping disorder are the most striking features in the two individuals concerned. TTI2, together with TTI1 and TELO2, encode proteins that constitute the triple T heterotrimeric complex. This TTT complex interacts with the HSP90 and R2TP to form a super-complex that has a chaperone function stabilizing and maturing a number of kinases, such as ATM and MTOR, which are key regulators of cell proliferation and genome maintenance. Pathogenic variants in TTI2 logically result in a phenotype close to that caused by TELO2 variants. This article is protected by copyright. All rights reserved.

KEYWORDS:

Premature ovarian failure; Recessive intellectual disability; TTI2; Triple T complex

PMID:
31290144
DOI:
10.1111/cge.13603

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