Format

Send to

Choose Destination
Eur J Hum Genet. 2019 Feb 15. doi: 10.1038/s41431-019-0358-9. [Epub ahead of print]

A novel variant of the human mitochondrial DnaJ protein, Tid1, associates with a human disease exhibiting developmental delay and polyneuropathy.

Author information

1
School of Neurobiology Biochemistry and Biophysics, Sagol School of Neurosciences, Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.
2
Department of Pediatrics, Makassed Hospital and Al-Quds Medical School, East Jerusalem, Palestinian Territories, Jerusalem, Israel. drbassam@hotmail.com.
3
Department of Pediatrics, Makassed Hospital and Al-Quds Medical School, East Jerusalem, Palestinian Territories, Jerusalem, Israel.
4
Monique and Jacques Roboh Department of Genetic Research, Hadassah, Hebrew University Medical Center, Jerusalem, Israel. elpeleg@hadassah.org.il.
5
Rappaport Faculty of Medicine, Technion, Israel Institute of Technology, Haifa, Israel.
6
Child Neurology and Development Center, Hillel-Yaffe Medical Center, Hadera, Israel.
7
School of Neurobiology Biochemistry and Biophysics, Sagol School of Neurosciences, Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel. azema@tauex.tau.ac.il.

Abstract

Here, we describe a single patient from a consanguineous family, who suffers from developmental delay, intellectual disability, hypermetropia, moderate alternating esotropia, unsteady gait, and peripheral polyneuropathy. Brain MRI revealed basal ganglia disease. Exome analysis disclosed a homozygous variant, c.452G>C (p.(Arg151Thr)), in TID1, encoding a mitochondrial J-protein chaperone that is known for its function in assisting the Hsp70 chaperone, mortalin, in mediating the refolding of denatured protein and dissolving protein aggregates. Results from in vitro import assays showed that both wild type and c.452G>C (p.(Arg151Thr)) are efficiently imported into isolated mitochondria. However, the import rate of the c.452G>C (p.(Arg151Thr)) variant was less than that of the wild-type protein. In the second part of this study, we demonstrated, in vitro, that the disaggregation function of the mortalin/Tid1 team is compromised in the TID1 c.452G>C (p.(Arg151Thr)) variant, as its chaperone activity has a level similar to that of the non-functional H→Q HPD domain variant. The results shed light on the essential function played by Tid1 during neuronal development.

PMID:
30770860
DOI:
10.1038/s41431-019-0358-9

Supplemental Content

Full text links

Icon for Nature Publishing Group
Loading ...
Support Center