2009 Vienna - European Society of Human Genetics

Cancer genetics
Vienna, Vienna, Austria.
Mutation screenings for confirmation of suspected diagnoses and for
verification of carrier status are an essential part of human genetic
diagnostics. The to-date “gold standard” in mutation analysis is direct
DNA sequencing, that allows analysis of single gene areas up
to lengths of several hundred bases. Analysis of many gene areas or
several complete genes for diagnostic reasons is very labor-intensive.
Thus tests enabling paralleled analysis at low cost and high flexibility
would be favourable.
The aim of this work was to evaluate the suitability of the mutationspecific
mutS protein for a DNA-microarray based mutation detection
method which enables highly-paralleled mutation detection. E. coli
mutS protein recognizes single point mutations, as well as insertions
and deletions of up to four base pairs and is thus usable for point mutation
testing. Using different recombinant mutS-constructs however
failed reliable mutation-testing on a DNA-microarray. However herewith
we provide a convenient control system for testing “Enzymatic
Mutation Detection” which could be helpful when trying other proteinbased
mutation tests upon DNA-chip hybridization using CEL1 endonuclease,
EndoV , bacteriophage resolvase T4 endonuclease VII and
T7 endonuclease I.
keywords: mutation testing, mutS, microarray
P06.063
increased risk of mB in heterozygous carriers of NBN gene
germline mutations
K. H. Chrzanowska, E. Ciara, D. Piekutowska-Abramczuk, E. Popowska, W.
Grajkowska, S. Barszcz, D. Perek, B. Dembowska-Bagińska, E. Kowalewska,
A. Czajńska, M. Perek-Polnik, M. Syczewska, K. Czornak, M. Krajewska-
Walasek, M. Roszkowski;
The Children’s Memorial Health Institute, Warsaw, Poland.
Cerebellar medulloblastoma (MB) is the most common highly malignant,
invasive embryonal brain tumor in children. Several signaling
pathways are known to be engaged in hereditary and sporadic MB.
Nibrin, a protein product of the NBN (formerly NBS1) gene is a component
of the Mre11/Rad50/Nbs1 complex that is critical for sensing
and processing double strand breaks in DNA, and is also required for
the proper initiation of base excision repair. Hypomorphic mutations in
the NBN gene are the cause of Nijmegen breakage syndrome (NBS),
a severe disease predisposing to different types of cancer, including
MB. The aim of our study was to identify NBN gene mutations and
to determine their frequency in Polish patients with different types
of sporadic medulloblastomas. A group of 110 patients with MB was
screened for mutations in the NBN gene by SSCP-PCR followed by
direct DNA sequencing. Seven heterozygous carriers of two various
germline NBN gene mutations (6.36%) were found: four with mutation
c.511A>G in exon 5 and three with mutation c.657_661del5 in exon
6. The risk of medulloblastoma was estimated as 2.89 (for c.511A