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The original PARK6 family (the Marsala kindred) and two other families, which this group has previously mapped to 1p36–35 by linkage analysis, were chosen for analysis by direct sequencing, to determine whether PARK6 was caused by D-1 mutations.

DNA was extracted from peripheral lymphocytes according to standard protocols.

Mutations in DJ-1 were discovered in two consanguineous families from geographically isolated regions in Europe.

This brings to five the number of genes reported that are directly implicated in Mendelian Parkinson’s disease.

Mutations in the DJ-1 gene have recently been shown to cause autosomal recessive Parkinson’s disease.

To estimate the prevalence of this mutation, an analysis was undertaken of 39 index cases of Parkinson’s disease in whom a family history suggested autosomal recessive inheritance.

To date, however, there have been no published data estimating DJ-1 prevalence in Parkinson’s disease.

The large cohort of autosomal recessive patients studied indicates that the frequency of pathogenic DJ-1 mutations is low in Parkinson’s disease, especially given that we excluded from analysis any known parkin gene mutations.

We also screened all our samples for the 14 kbp deletion reported by Bonifati At present the role of DNA diagnostic testing for mutations in DJ-1 is unclear, but these data suggest that such testing will not yield numerically significant results and therefore, unlike the parkin gene, DJ-1 is unlikely to be of clinical importance in neurological practice.

Two patients reported depression, but none suffered anxiety disorder, which has also been noted in DJ-1.

At the time of collection, some of these patients may not have had a full psychiatric history recorded.

We excluded cases known to have even a single parkin gene mutation, though seven of these patients had not had parkin gene analysis.

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