title: WES in a family trio suggests involvement of TECPR2 in a complex form of progressive motor neuron disease.
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.
authors.affiliation: Istituto Giannina Gaslini, Genova, Italy.
authors.forename: A E
authors.initials: AE
authors.lastname: Covone
authors.affiliation: Istituto Giannina Gaslini, Genova, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Fiorillo
authors.affiliation: Istituto Giannina Gaslini, Genova, Italy.|DINOGMI, Università degli Studi di Genova, Genova, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Acquaviva
authors.affiliation: Istituto Giannina Gaslini, Genova, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Trucco
authors.affiliation: Istituto Giannina Gaslini, Genova, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Morana
authors.affiliation: Istituto Giannina Gaslini, Genova, Italy.|DINOGMI, Università degli Studi di Genova, Genova, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Ravazzolo
authors.affiliation: Istituto Giannina Gaslini, Genova, Italy.|DINOGMI, Università degli Studi di Genova, Genova, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Minetti
mesh_terms: D000074183:ATPases Associated with Diverse Cellular Activities; D000293:Adolescent; D019943:Amino Acid Substitution; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; 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 / Q000235:genetics*; D008875:Middle Aged; D016472:Motor Neuron Disease / Q000235:genetics* / Q000473:pathology; D020125:Mutation, Missense; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D010375:Pedigree; D010641:Phenotype
chemical_list: D002352:Carrier Proteins; D009419:Nerve Tissue Proteins; C578280:TECPR2 protein, human; D008666:Metalloendopeptidases; C112889:SPG7 protein, human; D000074183:ATPases Associated with Diverse Cellular Activities
keywords: TECPR2; WES; autophagy; exome; missense variant; motor neuron disease