Patients and methods. The patient with ataxia where the SCA1 diagnosis was verified by polymerase chain reaction (PCR) (proband marked with an arrow in Fig. 1a) reported “similar cases” not only in his, but in another family in the same village. At the age of 27, this man felt gait instability and clumsiness of the hands. On admission, his hand and leg ataxia was accompanied with dysarthria, vertical nystagmus and brisk tendon reflex.  

After informed and written consent was obtained, a detailed history was taken from all available family members and they were videotaped and examined at home by at least two neurologists (MS and NS). Whenever possible, complete medical records of all family members were obtained. In the affected members we focused on the age at onset, initial signs and symptoms and, if the patient had passed away, cause and age at the time of death.

The same procedure was conducted for the identification and examination of the second family with “similar” problems from the same village. The first examined SCA1 male patient experienced gait instability at the age of 36 (proband marked with an arrow in Fig. 1b). On examination his gait ataxia was accompanied with ophthalmoparesis, dysarthria and brisk tendon reflexes. The age at onset was determined in affected relatives according to the previously described methodology [4]. Interviews with all members of both families failed to reveal any information on the marriages between their members in the last seven generations. Unfortunately, there were no genealogical records to further prove this point.

Samples of venous blood were taken for genetic diagnostics from all available members of both families. The number of CAG repeats in the SCA1 gene was determined by PCR followed by polyacrylamide gel electrophoresis (PAGE) [5]. PCR amplification of the D6S337 dinucleotide repeat locus was used for haplotype analysis, as this locus co-segregates with the SCA1 gene [6]. Demographic differences between two families were analyzed using the t-test.