Bi-allelic TARS Mutations Are Associated with Brittle Hair Phenotype.


Journal

American journal of human genetics
ISSN: 1537-6605
Titre abrégé: Am J Hum Genet
Pays: United States
ID NLM: 0370475

Informations de publication

Date de publication:
01 08 2019
Historique:
received: 28 03 2019
accepted: 24 06 2019
entrez: 3 8 2019
pubmed: 3 8 2019
medline: 17 3 2020
Statut: ppublish

Résumé

Brittle and "tiger-tail" hair is the diagnostic hallmark of trichothiodystrophy (TTD), a rare recessive disease associated with a wide spectrum of clinical features including ichthyosis, intellectual disability, decreased fertility, and short stature. As a result of premature abrogation of terminal differentiation, the hair is brittle and fragile and contains reduced cysteine content. Hypersensitivity to UV light is found in about half of individuals with TTD; all of these individuals harbor bi-allelic mutations in components of the basal transcription factor TFIIH, and these mutations lead to impaired nucleotide excision repair and basal transcription. Different genes have been found to be associated with non-photosensitive TTD (NPS-TTD); these include MPLKIP (also called TTDN1), GTF2E2 (also called TFIIEβ), and RNF113A. However, a relatively large group of these individuals with NPS-TTD have remained genetically uncharacterized. Here we present the identification of an NPS-TTD-associated gene, threonyl-tRNA synthetase (TARS), found by next-generation sequencing of a group of uncharacterized individuals with NPS-TTD. One individual has compound heterozygous TARS variants, c.826A>G (p.Lys276Glu) and c.1912C>T (p.Arg638

Identifiants

pubmed: 31374204
pii: S0002-9297(19)30242-3
doi: 10.1016/j.ajhg.2019.06.017
pmc: PMC6698936
pii:
doi:

Substances chimiques

Transcription Factor TFIIH 148710-81-0
Threonine-tRNA Ligase EC 6.1.1.3

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

434-440

Informations de copyright

Copyright © 2019 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

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Auteurs

Arjan F Theil (AF)

Department of Molecular Genetics, Oncode Institute, Erasmus University Medical Center, University Medical Center Rotterdam, 3015 GD Rotterdam, the Netherlands.

Elena Botta (E)

Istituto di Genetica Molecolare, Consiglio Nazionale delle Ricerche, 27100 Pavia, Italy.

Anja Raams (A)

Department of Molecular Genetics, Oncode Institute, Erasmus University Medical Center, University Medical Center Rotterdam, 3015 GD Rotterdam, the Netherlands.

Desiree E C Smith (DEC)

Metabolic Unit, Department of Clinical Chemistry, Amsterdam University Medical Center and Amsterdam Gastroenterology and Metabolism, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, 1081 HZ Amsterdam, the Netherlands.

Marisa I Mendes (MI)

Metabolic Unit, Department of Clinical Chemistry, Amsterdam University Medical Center and Amsterdam Gastroenterology and Metabolism, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, 1081 HZ Amsterdam, the Netherlands.

Giuseppina Caligiuri (G)

Istituto di Genetica Molecolare, Consiglio Nazionale delle Ricerche, 27100 Pavia, Italy.

Sarah Giachetti (S)

Istituto di Genetica Molecolare, Consiglio Nazionale delle Ricerche, 27100 Pavia, Italy.

Silvia Bione (S)

Istituto di Genetica Molecolare, Consiglio Nazionale delle Ricerche, 27100 Pavia, Italy.

Roberta Carriero (R)

Istituto di Genetica Molecolare, Consiglio Nazionale delle Ricerche, 27100 Pavia, Italy.

Giordano Liberi (G)

Istituto di Genetica Molecolare, Consiglio Nazionale delle Ricerche, 27100 Pavia, Italy.

Luca Zardoni (L)

Istituto di Genetica Molecolare, Consiglio Nazionale delle Ricerche, 27100 Pavia, Italy.

Sigrid M A Swagemakers (SMA)

Department of Pathology and Clinical Bioinformatics Unit, Erasmus University Medical Center, 3015 GD Rotterdam, the Netherlands.

Gajja S Salomons (GS)

Metabolic Unit, Department of Clinical Chemistry, Amsterdam University Medical Center and Amsterdam Gastroenterology and Metabolism, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, 1081 HZ Amsterdam, the Netherlands; Genetic Metabolic Diseases, Amsterdam University Medical Center, University of Amsterdam, 1081 HZ Amsterdam, the Netherlands.

Alain Sarasin (A)

Institut Gustave Roussy, UMR8200 CNRS, 94805 Villejuif, France.

Alan Lehmann (A)

Genome Damage and Stability Centre, School of Life Sciences, University of Sussex, Falmer, Brighton BN1 9RH, UK.

Peter J van der Spek (PJ)

Department of Pathology and Clinical Bioinformatics Unit, Erasmus University Medical Center, 3015 GD Rotterdam, the Netherlands.

Tomoo Ogi (T)

Department of Genetics, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan; Department of Human Genetics and Molecular Biology, Graduate School of Medicine, Nagoya University, Nagoya 464-0805, Japan.

Jan H J Hoeijmakers (JHJ)

Department of Molecular Genetics, Oncode Institute, Erasmus University Medical Center, University Medical Center Rotterdam, 3015 GD Rotterdam, the Netherlands; Princess Maxima Center for Pediatric Oncology, Oncode Institute, 3584 CS Utrecht, the Netherlands; CECAD Forschungszentrum, University of Cologne, 50931 Cologne, Germany.

Wim Vermeulen (W)

Department of Molecular Genetics, Oncode Institute, Erasmus University Medical Center, University Medical Center Rotterdam, 3015 GD Rotterdam, the Netherlands. Electronic address: w.vermeulen@erasmusmc.nl.

Donata Orioli (D)

Istituto di Genetica Molecolare, Consiglio Nazionale delle Ricerche, 27100 Pavia, Italy. Electronic address: orioli@igm.cnr.it.

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