Glucocerebrosidase gene variants in parkinsonian patients with Machado Joseph/spinocerebellar ataxia 3.

UNLABELLED: Machado-Joseph disease/spinocerebellar ataxia type 3 (MJD/SCA3) may rarely presents a parkinsonian phenotype. Considering that mutations in the glucocerebrosidase (GBA) gene have been associated with Parkinson disease, we investigated whether these would be more prevalent in MJD/SCA3 patients with parkinsonian manifestations than in those without them. METHODS: MJD/SCA3 patients with parkinsonian features were identified and compared to relatives and to a MJD/SCA3 control group with no such features. The GBA gene was sequenced and, in a subset of patients and in normal volunteers, GBA enzyme activity was measured. RESULTS: We have identified nine index MJD/SCA3 patients with parkinsonian manifestations. Overall, GBA sequence variations were found in 3/9 MJD/SCA3 index cases with parkinsonian manifestations (33%) and in 0/40 MJD/SCA3 controls without parkinsonism (p=0.03, Fisher exact test). The GBA sequence variations found were p.K(-27)R, p.E326K, and p.T369M. The latter two sequence variations were also found in two symptomatic relatives with no parkinsonian manifestations. A MJD/SCA3 relative belonging to the first positive pedigree and carrier of the p.K(-27)R mutation also presented parkinsonian manifestations. GBA activity in MJD/SCA3 patients was similar to those found in the normal control group. CONCLUSION: Sequence variations at the GBA gene may play a role as a minor, modifying gene of MJD/SCA3 phenotype. This hypothetical role was not related to changes in GBA activity in peripheral leukocytes.

Histopathological changes in avian kidney caused by Bothrops insularis (jararaca ilh a) venom and a phospholipase A2-containing fraction.

The histopathological changes induced in avian kidney by the intramuscular injection of Bothrops insularis (jararaca ilh a) venom and its phospholipase A2 (PLA2)-containing fraction were examined. Acute experiments (3 h and 24 h) with B. insularis crude venom (20 microg and 80 microg) or its PLA2-contaning fraction (10 microg and 40 microg) resulted in significant structural damage to the kidneys of 5-12-day-old chicks. Histopathological analysis indicated that the venom and its fraction acted on the renal tubules and glomeruli. The morphological changes, although widespread, varied in intensity from cell to cell, and from tubule to tubule in venom-injected chicks. The tubular and glomerular changes produced by the venom and its PLA2-containing fraction may be the result of a direct cytotoxic effect potentiated by ischemia-related disturbances in the regional hemodynamics. The venom and its fraction affected more segments along reptilian-type nephrons than along mammalian ones. This divergent sensitivity to the venom and its fraction may reflect the species-specific characteristics of B. insularis snake, an example of geographical isolation influencing its diet which is almost exclusively avian.