Genetic background of Huntington disease in Croatia: Molecular analysis of CAG, CCG, and ?2642 (E2642del) polymorphisms

• Published in: Human mutation Vol. 20; no. 3; p. 233
• Main Authors: He?imovi?, Silva, Klepac, Nata?a, Vla?i?, Jelena, Vojta, Aleksandar, Janko, Dolores, ?karpa-Prpi?, Ingrid, Canki-Klain, Nina, Markovi?, Dubravko, Bo?ikov, Jadranka, Relja, Maja, Paveli?, Kre?imir
• Format: Journal Article
• Language: English
• Published: Hoboken Hindawi Limited 01.09.2002
• ISSN: 1059-7794; 1098-1004
• DOI: 10.1002/humu.9055

This study presents the first molecular data on the basis and the origin of Huntington disease in Croatia and is the first such analysis performed among a Slavic population. We analyzed three trinucleotide polymorphisms in the HD gene: CAG, CCG and GAG [Delta]2642 (E2642del) triplets. Analysis of the CAG repeat size among 44 Huntington patients (39-66 CAGs) and 51 normal individuals (9-34 CAGs) showed that the range of the repeats was similar to previous findings. The frequency of the CCG and [Delta]2642 polymorphic alleles on N and HD chromosomes was found to correlate well with earlier reports for Western European populations. We found significance for both the CCG7 allele (p=0.004) and the [Delta]2642 allele (p<0.001) among HD chromosomes. The CCG7 allele was overpresented among affected chromosomes (94.6%), but was also the most frequent CCG allele among normal chromosomes (66.7%). Interestingly, the [Delta]2642 allele was present on 40.5% HD chromosomes compared to only 9.8% of control chromosomes. Our results indicate that HD mutations in Croatia could be of the same origin as in Western populations and also support the multi-step hypothesis for generating new HD alleles. Similar frequencies and distributions of both the CCG and the [Delta]2642 polymorphisms in Croatia and Western European normal chromosomes indicate that the prevalence rate of HD in Croatia may be as high as in Western populations. Since we estimated a lower prevalence rate (1 : 100,000), we assume that there are still many misdiagnosed and/or unrecognized cases of Huntington disease in Croatia. © 2002 Wiley-Liss, Inc.