Autosomal recessive juvenile parkinsonism (AR-JP, PARK2; OMIM 602544), one of the monogenic forms of Parkinson's disease (PD), was initially described in Japan. It is characterized by early onset (before age 40), marked response to levodopa treatment and levodopa-induced dyskinesias. The gene responsible for AR-JP was recently identified and designated parkin. We have analysed the 12 coding exons of the parkin gene in 35 mostly European families with early onset autosomal recessive parkinsonism. In one family, a homozygous deletion of exon 4 could be demonstrated. By direct sequencing of the exons in the index patients of the remaining 34 families, eight previously undescribed point mutations (homozygous or heterozygous) were detected in eight families that included 20 patients. The mutations segregated with the disease in the families and were not detected on 110-166 control chromosomes. Four mutations caused truncation of the parkin protein. Three were frameshifts (202-203delAG, 255delA and 321-322insGT) and one a nonsense mutation (Trp453Stop). The other four were missense mutations (Lys161Asn, Arg256Cys, Arg275Trp and Thr415Asn) that probably affect amino acids that are important for the function of the parkin protein, since they result in the same phenotype as truncating mutations or homozygous exon deletions. Mean age at onset was 38 +/- 12 years, but onset up to age 58 was observed. Mutations in the parkin gene are therefore not invariably associated with early onset parkinsonism. In many patients, the phenotype is indistinguishable from that of idiopathic PD. This study has shown that a wide variety of different mutations in the parkin gene are a common cause of autosomal recessive parkinsonism in Europe and that different types of point mutations seem to be more frequently responsible for the disease phenotype than are deletions.
A field experiment of novel systematic design was established on 17 sites in the three years 1988-90 to compare the effect of spray timing on the disease control provided by fungicides. At each site one set of plots received applications of a mixture of fenpropimorph and prochloraz or triadimenol, tridemorph and chlorothalonil fungicides, applied at successively later start dates to produce a series of temporally and spatially related, but discrete, epidemics curtailed at consecutively later stages of development between GS32 and GS75. A second set of plots was treated with a single spray of one of a set of the nine candidate fungicides between GS32 and GS71. Disease developed at each site, with moderate septoria leaf spot (Septoria tritici) at five of the eight sites in 1988 and four of the seven sites in 1989. Erysiphe graminis f.sp. tritici was present at two sites in 1988, four sites in 1989 and one site only in 1990. Puccinia striiformis (four sites only in 1989 and 1990) and brown rust (one site in each year) were less common. The systematic treatments showed consistent relationships between green leaf retention during grain filling and yield. They also provided clear indications that epidemics of foliar disease initiated before flag leaf emergence had the greatest impact on yield. After this stage, yield loss averaged 27·2 kg ha ¹1 for each day that elapsed before fungicide was applied. The sequential single spray treatments showed marked differences between the protectant and eradicant activity of the different fungicides used. Each disease was most effectively controlled on the final leaf by treatment at or immediately after its emergence. Chlorothalonil was as effective as any of the fungicides tested against septoria, when applied before flag leaf emergence, but was inferior when applied after this stage. The fungicides were equally effective against yellow rust when applied just before symptoms were detected, when spray timing appeared to be more important than choice of fungicide. The response of brown rust to fungicides was similar, except that chlorothalonil was the least effective. For mildew, timing seemed to be less important, although sprays applied immediately after leaf emergence provided the best control on each individual leaf layer. Yield was well related to disease and green leaf area late in the season, these factors being more important than which disease was present, which fungicide, and which cultivar were used.
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