Biallelic TOR1A mutations cause severe arthrogryposis: A case requiring reverse phenotyping

Eur J Med Genet. 2019 Sep;62(9):103544. doi: 10.1016/j.ejmg.2018.09.011.

Esra Isik ¹, Ayca Aykut ², Tahir Atik ³, Ozgur Cogulu ⁴, Ferda Ozkinay ⁴

Affiliations

1 Subdivision of Pediatric Genetics, Department of Pediatrics, Faculty of Medicine, Ege University, Izmir, Turkey. Electronic address: esra.isik@ege.edu.tr.
2 Department of Medical Genetics, Faculty of Medicine, Ege University, Izmir, Turkey.
3 Subdivision of Pediatric Genetics, Department of Pediatrics, Faculty of Medicine, Ege University, Izmir, Turkey.
4 Subdivision of Pediatric Genetics, Department of Pediatrics, Faculty of Medicine, Ege University, Izmir, Turkey; Department of Medical Genetics, Faculty of Medicine, Ege University, Izmir, Turkey.

PMID: 30244176 DOI: 10.1016/j.ejmg.2018.09.011

Abstract

Heterozygous mutations in TOR1A gene are known to be responsible for DYT1 dystonia with incomplete penetrance. Autosomal recessive TOR1A disease is a very recently described syndrome characterized by severe arthrogryposis, developmental delay, strabismus and tremor. A 2 month-old boy with severe arthrogryposis and developmental delay was referred to our department for genetic counseling. Dystonic movements were observed on physical examination. Whole exome Sequencing revealed a homozygous nonsense variant in exon 5 of TOR1A (c.862C > T, p.Arg288*). Our results expand the phenotypic and mutational spectrum of biallelic TOR1A disease, while emphasizing the importance of reverse phenotyping in the diagnosis of rare genetic disorders.

Keywords

Biallelic mutations; Reverse phenotyping; Severe arthrogryposis; TOR1A.

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