• Amelia Conte, Serena Lattante, Marco Luigetti, Alessandra Del Grande, Angela Romano, Alessandro Marcaccio, Giuseppe Marangi, Paolo Maria Rossini, Giovanni Neri, Marcella Zollino, and Mario Sabatelli.
• Istituto di Neurologia, Università Cattolica del Sacro Cuore, Rome, Italy.
• J. Neurol. Neurosurg. Psychiatr. 2012 Dec 1; 83 (12): 1201-3.

ObjectiveTo classify familial amyotrophic lateral sclerosis (FALS) on the base of family history, and to determine whether frequency of mutations in major amyotrophic lateral sclerosis (ALS) genes varies in different FALS categories.MethodsIncluded in the study are 53 FALS families. Patients were classified as definite, probable and possible FALS, according to recently proposed criteria. Seven ALS-associated genes, including SOD1, TARDBP, FUS, ANG, ATXN2, OPTN and C9ORF72, were analysed.ResultsThirteen patients (24.5%) were included in the definite group. The great majority of our FALS cases (40/53, 75.5%) were families with only two affected relatives; of these, 31 (58.5%) were included in the probable, and 9 (17%) in the possible FALS categories. The percentage of mutations was 61.5% in definite, 41.9% in probable and 11.1% in possible FALS. With respect to probable FALS, if cases with parent-to-child transmission of the disease were considered separately, the mutational load increased to 61.5%, as observed in definite FALS.ConclusionsOur findings provide evidence that frequency of mutations in currently known ALS genes varies widely among different FALS categories. Families with only two affected relatives have heterogeneous genetic components, the chance to detect mutations being higher in cases with parent-to-child transmission.

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