Tassin et al. (1998) found linkage of the gene for PDJ to 6q25.2-q27 in one Algerian and 10 European multiplex families. They found the clinical spectrum of the disease in these families, with age at onset up to 58 years and the presence of painful dystonia in some patients, to be broader than that reported previously. In all patients examined, 2 of the 3 cardinal signs of PD (akinesia, rigidity, and tremor) were found. Marked improvement with levodopa treatment occurred in all except two untreated secondary cases found in family studies. Age at onset was less than 40 years for at least one affected sib. Later, Lucking et al. (1998) found a novel homozygous deletion of exons 8 and 9 of the PARK2 gene in this Algerian family.

Myhre et al. (2008) investigated the significance of parkin and PINK1 mutations in the region by examining families from Jordan with a high incidence of consanguineous marriages, a recessive pattern of inheritance, and at least one patient with parkinsonism in each family. This study included 11 consanguineous families with 1-2 affected subjects with juvenile or young-onset parkinsonism. In total, the study group comprised of 17 affected members among 59 family members. Five families had only one affected member strictly classified as having young-onset sporadic parkinsonism. The age at onset was found to be on average 26.8 ± 5.8 years [range 19-36] covering cases defined as either young (? 21 and <40) or juvenile (<21) onset. The parents were unaffected with the absence of disease in several generations suggesting an autosomal recessive mode of inheritance. Clinical manifestations included marked response to levodopa (60%), sleep benefit (95%), observed L-dopa induced dyskinesia (90%), dystonic posture (90%), and a slow disease progression (90%). At the molecular level, a three-generation family was identified with an exon 4 deletion in the parkin gene segregating with the disease. Both affected members were homozygous for the deletion that segregated on one haplotype that spanned the gene. Exon dosage analysis confirmed the recessive pattern of inheritance with heterozygous deletions segregating in healthy family members. Myhre et al. (2008) also identified two different mutations in the PINK1 gene in two families. Additionally, Myhre et al. (2008) identified common polymorphisms in the two genes and these polymorphisms were found to be co-segregating within families. Myhre et al. (2008) concluded that the results obtained from this study further extend on the involvement of PINK1 mutations in recessive early-onset parkinsonism with clinical features similar to carriers of parkin mutations.

Gouider-Khouja et al. (2003) reported the clinical, pathological and genetic findings in three siblings with autosomal recessive juvenile parkinsonism (AR-JP) linked to Parkin gene. The first patient was the first child of a consanguineous mating and had two affected sisters and one unaffected brother. Examination at age 35 showed isolated Parkinsonian syndrome with rest tremor, bradykinesia, and rigidity predominating in the right side. At age 47, he presented fever, left hemiplegia, and drowsiness which rapidly led to coma and he died. Autopsy was performed eight hours after death and the coronal section of the hemispheres showed an edematous area in the right temporal lobe with marked flattening of the gyri and numerous petechial hemorrhages. Light microscopy examination showed a right temporal abscess. The patient had extensive neuronal loss. His sister was 41 years old and complained of rest tremor of the left hand at age 21 years. Her neurological examination at age 23 showed a Parkinsonian syndrome predominating in the left side. Treatment was started at age 39 which showed an improvement for her case. The youngest of the three siblings was examined at 25 years. She complained of rest tremor of the left hand for six months. Clinical examination revealed akineto-rigid and tremorous left hemiparkinsonian syndrome. Dystonia of the right side was observed one year after onset.