Endocrine Abstracts (2006) 11 P527

Origin and spread of the SDHD p.Y114C mutation causing head and neck paraganglioma in Trentino, Italy

F Schiavi1, Z Erlic1, T Savvoukidis1, S Demattè2, A Del Piano2, ME Cecchini2, P Amistà1, F Grego1, F Trabalzini1, M Hoffman3, A Schwentek3, F Mantero1, F Branz2, HPH Neumann3 & G Opocher1

1University of Padova, Padova, Italy; 2S.Chiara Hospital, Trento, Italy; 3Albert Ludwigs University, Freiburg, Germany.

Head and neck paragangliomas (HNPs) are tumors derived from the neuroectoderm. HNPs are generally hormonally silent and often asymptomatic. They can be part of the Pheochromocytoma/ Paraganglioma Syndrome, due to mutations of SDHB, SDHC and SDHD genes. SDHD founder effects have been described in the Netherland, USA, Italy and Spain.

We identified a new founder effect in a small geographic area (Valsugana-Trentino, actually 50.000 inhabitants), with high anecdotic incidence of HNP. Twelve unrelated kindreds with HNP presented the SDHD c.341G>C p.Y114C mutation.

We extended the genealogies and draw some of the family tree up to 1750 without identifing a common ancestor.

Haplotype have been studied using 5 polymorphic markers spanning 360 kb around SDHD gene. A conserved haplotype was identified in SDHD c.341G>C chromosomes from the Trentino families suggesting the occurence of a common founder.

The SDHD c.341G>C mutation was present also in 4 German and 1 Polish families. Two German families presented the same haplotype, instead it was different in the Polish family and in other two German families. The three haplotypes probably derived from a single ancestral haplotype, as the differences among them could be explained with one independent recombination event in each.

There could be an ancient link between Italian, German and Polish families: one of the three valley in which we identified this founder effect, named Val dei Mocheni, was settled in the 13th century by German farmers, originary from Baviera and Boemia. This comunity never integred in the social environment, and the dialect they currently speak derive from the ancient German language.

We hypothesize that a German ancestor with the SDHD c.341G>C mutation was part of the group who settled the Val dei Mocheni, and that the cultural and geographical isolation caused the bottleneck effect, explaining the spread of SDHDc.341G>C-linked HNPs in this population.