Naslov
ALS with variable phenotypes in a six-generation family caused by leu144phe mutation in the SOD1 gene

Autori
Mase, G. ; Ros, S. ; Gemma, A. ; Bonfigli, L. ; Carraro, N. ; Cazzato, G. ; Rolfo, M. ; Zanconati, F. ; Sepčić, Juraj ; Jurjević, A. ; Pirulli, D. ; Boniotto, M. ; Zezlina, S. ; Crovella, S. ; Amoroso, A.

Izvornik
Journal of the Neurological Sciences (0022-510X) 191 (2001), 1-2; 11-118

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
Amyotrophic lateral sclerosis; Istro-rumanian; SOD1 gene

Sažetak
Background: amyotrophic lateral sclerosis(ALS)is a progressive neurological disorder. The mutation of Cu/Zn superoxide dismutase gene(SOD1) are responsible for familial ALS.We investigated a large family of Istro-Rumanian origin characterized by an autosomal dominant ALS occuring in 18 cases(three of which are still alive) throughout six generations. Methods: clinical data were available for nine patients from the 2nd generation onward, among which one contained the neuropathological details. The mean age at onset of the disease(SD)was 57.3+/-8.9 years(range 49-72), while the duration of the disease spanned over a length of time equal to 4.9+/-1.96 years(range 1.5-7). The analysis of the coding region of SOD1 was done by PCR and direct sequencing. The SOD1 activity was measured by using the red and mononuclear cells belonging to three of the patients. Results: the leu144phe mutation of SOD1 was identified in four patients while a normal sequence was found in five healthy related subjects. The molecular defect was responsible for a decrease in SOD1 activity. Most of patients in this family presented clinical manifestations of ALS(in particular, the lower limb onset variant)not as severe as typical ALS caused by other SOD1 mutations.However, one patient suffering from hyperthyroidism for 17years, showed an early onset and a rapidly progressing ALS coupled with dementia. Conclusions: we described a large family with a relatively not severe phenotype of ALS(due to a leu144phe SOD1 mutation)that was compromised in one patient by a concomitant hyperthyroidism.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti, Kliničke medicinske znanosti

POVEZANOST RADA