JIMD Reports, Volume 22

Anna Ardissone, Tiziana Granata, Andrea Legati, Daria Diodato, Laura Melchionda, Eleonora Lamantea, Barbara Garavaglia, Daniele Ghezzi, Isabella Moroni, Ardissone, Anna, Granata, Tiziana, Legati, Andrea, Diodato, Daria, Melchionda, Laura, Lamantea, Eleonora, Garavaglia, Barbara, Ghezzi, Daniele, Moroni, Isabella

We report about a patient with infantile-onset neurodegenerative disease associated with isolated mitochondrial respiratory chain complex III (cIII) deficiency. The boy, now 13 years old, presented with language regression and ataxia at 4 years of age and then showed a progressive course resulting in the loss of autonomous gait and speaking during the following 2 years. Brain MRI disclosed bilateral striatal necrosis. Sequencing of a panel containing nuclear genes associated with cIII deficiency revealed a previously undescribed homozygous rearrangement (c.782_786delinsGAAAAG) in TTC19 gene, which results in a frameshift with premature termination (p.Glu261Glyfs(*)8). TTC19 protein was absent in patient's fibroblasts. TTC19 encodes tetratricopeptide 19, a putative assembly factor for cIII. To date TTC19 mutations have been reported only in few cases, invariably associated with cIII deficiency, but presenting heterogeneous clinical phenotypes. We reviewed the genetic, biochemical, clinical and neuroradiological features of TTC19 mutant patients described to date.