Autosomal recessive parkinsonism linked to parkin gene in a Tunisian family. Clinical, genetic and pathological study.

Objectives: To report clinical, pathological and genetic findings in a Tunisian kindred with autosomal recessive juvenile parkinsonism (AR-JP) linked to parkin gene.

Background: AR-JP has been mapped to chromosome 6q and is caused by several mutations of the parkin gene (Park 2). Pathological features in AR-JP are characterized by neuronal loss in substantia nigra (SN) without Lewy bodies (LB).

Ganglioside-induced differentiation-associated protein-1 is mutant in Charcot-Marie-Tooth disease type 4A/8q21.

We previously localized and fine-mapped Charcot Marie Tooth 4A (CMT4A), the autosomal recessive, demyelinating peripheral neuropathy, to chromosome 8. Through additional positional cloning, we have identified a good candidate gene, encoding ganglioside-induced differentiation-associated protein-1 (GDAP1). We found three different mutations in four different Tunisian families-two nonsense and one missense mutation.