Mendelian diseases and conditions in Croatian island populations: historic records and new insights

Abstract

Among Croatian islands, there are several which are known for unusual autochthonous diseases and specific medical conditions that result from the reproductive isolation and specific population genetic structure. These populations are characterized by high degree of genetic isolation, consanguinity, and inbreeding. The reported diseases include Mal de Meleda on Mljet island, hereditary dwarfism on Krk island, familial learning disability on Susak island, familial ovarian cancer on Lastovo island, and several other rare diseases and conditions inherited in Mendelian fashion. We present a historical perspective on how these conditions were first described, interpreted, and assessed. We reviewed the information obtained through genetic research in the past several years, when the genetic etiology of some of these conditions was explained. The disease gene causing Mal de Meleda was first localized at 8q chromosome, and mutations in the ARS (component B) gene encoding SLURP-1 (secreted mammalian Ly-6/uPAR-related protein 1) protein were identified subsequently. The genetic etiology of dwarfism on the island of Krk is explained by a mutation in the PROP1 gene, responsible for the short stature. The search for mutations underlying other monogenic diseases in Croatian islands is under way.

Figure 1

Effect of PROP-1 mutation on height in Jurandvor/Baščanska Draga (V11) population isolate in comparison to other investigated population isolates: Rab, Banjol, Barbat, Supetarska Draga, Lopar, Mljet, Lastovo, Vis, Komiža, and Susak (V1-V10). Dashed line – Jurandvor/Baščanska Draga (V11), females (n=151); full line – other villages (V1-V10), males (n=455); dotted line – Jurandvor/Baščanska Draga (V11), males (n=107); dot-dash line – other villages (V1-V10), females (n=546) (42).

Figure 2

Kinship estimates of ovarian cancer cases (black circles) and of the remaining population of the island of Lastovo (white circles) and in five generation of their ancestors; all differences were statistically significant at the level P<0.05 (56).