**7. Optineurin**

Optineurin is an inhibitor protein that play an important role in the maintenance of the Golgi complex, in membrane trafficking and in exocytosis. Alternative splicing results in multiple transcript variants encoding the same protein., three different isoforms are known.

#### **7.1. Genotype**

The human *OPTN* gene (Entrez Gene ID 10133) is located on chromosome 10p13, and it codes for a protein of 577 amino acids. In 2010 *OPTN* mutations have been described, for the first time, in ALS patients [63]. In the first paper about OPTN mutation three type of mutation have been found, two point mutation and one deletion. In 2011, a screening in the Caucasian population in SALS and FALS patients showed that *OPTN* mutations causing ALS are rare, especially in mainly Caucasian ALS subjects [64]. About Italian population, Del Bo and collaborators screened 274 ALS patients, 161 FALS and 113 SALS and the results showed six novel variants in both FALS and SALS patients, all occurring in an heterozygous state [13]. This data support the involvement of *OPTN* in ALS, especially in FALS patients, due to the 1.2% cases found mutated [13].

#### **7.2. Phenotype**

Del Bo et al. [13] suggested that ALS patients carrying OPTN mutations showed a prevalent lower-limb onset, with large variable age of onset (from 24 to 71 years of age) and progression (very aggressive forms with survival time < 1 year and very slow disease course over 10 years) with no differencies between SALS and FALS patients. Many patients were characterized by a prevalence of upper motor neuron signs.
