Screening of CHCHD10 in an Italian cohort of ALS/ALS-FTD patients (P2.051)

OBJECTIVE To screen CHCHD10 in an Italian cohort of sporadic and familial ALS, FTD and ALS-FTD patients. BACKGROUND Several reports have recently identified CHCHD10 mutations underlining heterogeneous motor neuron phenotypes. CHCHD10 encodes for a mitochondrial intermembrane space protein, likely involved in the assembly of respiratory chain. The original paper described a French family presenting ALS-FTD, cerebellar signs and sensorineural hypoacusia. Further mutations were observed in familial German, Finnish and North American cases, as well as in sporadic ALS (sALS) patients (mostly with bulbar onset). CHCHD10 involvement was also described in a family affected with apparent pure mitochondrial myopathy. DESIGN/METHODS We screened CHCHD10 in 222 sALS patients (11 of which FTD-ALS), 16 familial ALS and 1 familial ALS-FTD cases. RESULTS: We disclosed the novel heterozygous transition c.239C>T (p.Pro80Leu) in a male patient presenting with flail arms ALS at 25 years, evolving, in the course of eight years, in severe flaccid tetraparesys with respiratory involvement. Muscle biopsy revealed severe histochemical COX deficiency and impaired respiratory chain activity. This variant was also observed in a sporadic patient who developed classical ALS. Finally, a woman who developed bulbar ALS without cognitive impairment at 75 years harbored a mutation (c.100C>T, p.Pro34Ser) previously reported in two French sporadic FTD-ALS patients. No variants were identified among familial cases. CONCLUSIONS This study confirms the modest but not negligible incidence of CHCHD10 mutations also in Italian ALS/ALS-FTD sporadic patients. The incidence of this gene in our cohort was slightly lower compared to recent reports (1.4[percnt] versus 2.6[percnt]). All the mutations so far reported lie in a conserved region of the exon 2. Muscle mitochondrial abnormalities were observed in a patient of our cohort but they do not seem a peculiar feature of CHCHD10 pathology. Further studies are required to address the role of CHCHD10 in motor neuron disease. Disclosure: Dr. Riboldi has nothing to disclose. Dr. Ronchi has nothing to disclose. Dr. Del Bo has nothing to disclose. Dr. Ticozzi has nothing to disclose. Dr. Scarlato has nothing to disclose. Dr. Galimberti has nothing to disclose. Dr. Del Menico has nothing to disclose. Dr. Brajkovic has nothing to disclose. Dr. Corti has nothing to disclose. Dr. Silani has nothing to disclose. Dr. Bresolin has nothing to disclose. Dr. Comi has nothing to disclose.