WES in a family trio suggests involvement of TECPR2 in a complex form of progressive motor neuron disease.
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.
['Covone|A E|AE|', 'Fiorillo|C|C|', 'Acquaviva|M|M|', 'Trucco|F|F|', 'Morana|G|G|', 'Ravazzolo|R|R|', 'Minetti|C|C|']
D000074183:ATPases Associated with Diverse Cellular Activities D000293:Adolescent D019943:Amino Acid Substitution D001483:Base Sequence D002352:Carrier Proteins D018450:Disease Progression D059472:Exome D005260:Female D015870:Gene Expression D005808:Genes, Recessive D006579:Heterozygote D059014:High-Throughput Nucleotide Sequencing D006801:Humans D008297:Male D008666:Metalloendopeptidases D008875:Middle Aged D016472:Motor Neuron Disease D020125:Mutation, Missense D009419:Nerve Tissue Proteins D009474:Neurons D010375:Pedigree D010641:Phenotype
WES TECPR2 motor neuron disease exome missense variant autophagy