WES in a family trio suggests involvement of TECPR2 in a complex form of progressive motor neuron disease. Issue 2 (10th February 2016)

• Record Type: Journal Article
• Authors: Covone, A.E.; Fiorillo, C.; Acquaviva, M.; Trucco, F.; Morana, G.; Ravazzolo, R.; Minetti, C.
• Is Part Of: Clinical genetics. Volume 90:Issue 2(2016)
• Page Start: 182
• Page End: 185
• Publication Date: 2016-02-10
• Subjects: autophagy -- exome -- missense variant -- motor neuron disease -- TECPR2 -- WES; Medical genetics -- Periodicals; 616.0420
• DOI: 10.1111/cge.12730
• Languages: English
• ISSNs: 0009-9163

Abstract

Abstract : We have performed whole‐exome sequencing in a family trio with a 16‐year‐old girl suffering of progressive motor neuron disease. There was no family history of the disease and no parental consanguinity. Our exome analysis indicated the proband as a compound heterozygote for two missense variants in the TECPR2 gene according to a recessive mode of inheritance. The TECPR2 gene has been reported as a positive regulator of autophagy which is an essential mechanism for maintaining neuron homeostasis and survival and plays a key role in major adult and pediatric neurodegenerative diseases. Variants in this gene have been found responsible for a recently described form of hereditary spastic paraplegia called SPG49 in two previous reports. We propose that both variants causing amino acid substitution, p.Leu684Val and p.Thr903Met, inherited in trans‐phase compound heterozygote form, can be responsible for the phenotype observed in our patient. We also consider the possible contribution of a heterozygous variant in the SPG7 gene. Sanger sequencing confirmed the segregation of variants within the family tree including the patient's unaffected brother. Abstract :