Wolfram syndrome epidemiology: a hot-spot area in north-eastern Sicily

Background: According to the few available epidemiological studies Wolfram syndrome (WS) prevalence ranges from 1:100 000 in North-America to 1:805 000 in North India. Objective and hypotheses: The main purpose of this study was to ascertain WS prevalence in a district of North-eastern Sicily, i.e. a geographic area where consanguineous unions are not very unusual, particularly in the mountain villages of the hinterland. Methods: Prevalence rates were calculated by considering both the total population of our district (653 737) and the populations included within the 0-30 year age range (202 681). Furthermore, we also estimated the relative prevalence of WS among patients with youth-onset insulin-dependent DM of the Messina district who are currently aged under 30 years (256). Results: According to our findings, the global WS prevalence in our district is 1: 54 478, whereas its prevalence among individuals under 30 is 1: 16 890 and its relative prevalence among patients with juvenile-onset insulin-dependent diabetes mellitus is 1: 22.3. Seven of the 12 WS patients included in our study population came from the same small town in the Nebrodi Mountains and descended from two common ancestors. These 7 patients were born to 3 first cousin couples and exhibited the same homozygous frameshift/truncation mutation (Y454_L459del_fsX454). This same mutation was detected in other 2 sisters belonging to another, unrelated family, whereas the remaining 3 patients came from other 3 unrelated families and were heterozygotes for other 3 different mutations. The proportion of affected siblings in the context of their families was 0.50. Conclusions: WS prevalence may significantly change in different ethnic groups, as in the case of other genetically inherited diseases and it is possible to find hot-spot areas in regions where consanguineous unions are not infrequent