Method for the determination of data for the preparation of the diagnosis of phakomatosis

Abstract

The invention concerns a method for the determination of data for the preparation of presymptomatic or prenatal diagnosis of phakomatosis, in particular, a tumor suppressor gene disease, in a high-risk patient, in particular of neurofibromatosis, comprising the steps of: making available the tumor material from a person afflicted with the tumor suppressor gene disease, who is a relative of the high-risk patient; isolating tumor DNA from the tumor in the relative; isolating blood DNA from the blood of the relative; amplifying polymorphous DNA microsatellite markers from the tumor and the blood; separating the markers by length; observing the lengths of the markers; comparing the markers from the blood and the tumor; examining for a loss of alleles; optionally, comparing amplified markers from a second tumor of the relative; and amplifying polymorphous DNA microsatellite markers from the blood of an offspring and separating and observing the markers.

Description

FIELD OF THE INVENTION[0001]The invention concerns a method for the determination of data for the preparation of the presymptomatic or prenatal diagnosis of phakomatosis, in particular of tumor suppressor gene diseases, in particular of neurofibromatosis (type 1, type 2). Such methods are useful for children of parents suffering from a hereditary disease or their grandchildren to increase the probability of early detection of a new occurrence of the hereditary disease, or (if possible) of prenatal evaluation.BACKGROUND OF THE INVENTION[0002]The current state of the art for the preparation of the corresponding diagnosis, for this purpose, uses a mutation analysis of the DNA section coding for the characterizing gene for the hereditary disease. These tumor suppressor gene diseases include the autosomal dominant inherited neurofibromatoses.[0003]Neurofibromatosis occurs in two types, the peripheral type, called type 1, which represents approximately 85% of the cases, and the “central t...

AI Technical Summary

Benefits of technology

[0006]An advantage of the method according to the invention, in particular, is that it can be carried out very quickly. Thus, in all cases, the method according to the invention can be carried out in less than 2 weeks; moreover, if the procedure is accelerated, it can be carried out in approximately two days. The rapidity of the method according to the invention is particularly important in prenatal diagnosis. Moreover, the method according to the invention is also considerably more cost effective because of its simplicity than the mutation analysis known from the state of the art.

[0016]If, in the present case, the parent who is not affected has the allele A or C, then it is clear the allele A could only have originated from the unaffected parent. Similarly it would be clear in this example that allele B, which is probably exclusively responsible for the disease of the affected parent, was inherited by the child. In this case the child would have an increased risk of having the disease. In the case of NF2, it has been shown to be advantageous to use at least one of the markers CRYB2, D22S275, NF2CA3, D22S268, D22S430.

Problems solved by technology

The drawback of the mutation analysis is that it is very time consuming.

In addition, one drawback of the known mutation analysis is that in high-risk individuals the diagnosis can only be considered to have been confirmed by molecular genetic means if a mutation is found in the afflicted individual.

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