7 research outputs found
Potential mechanisms of attenuation for rifampicin-passaged strains of Flavobacterium psychrophilum
German Cockroaches (Blattella Germanica L.) as a Potential Source of Pathogens Causing Nosocomial Infections
A large germline deletion in the Chek2 kinase gene is associated with an increased risk of prostate cancer
Germline mutations in the von Hippel-Lindau (VHL) gene in patients from Poland: disease presentation in patients with deletions of the entire VHL gene
\u2022 Thirty-four Polish families with a clinical diagnosis of
VHL disease were studied in order to describe: (1) the
frequency of germline mutations in these families; (2) the
spectrum of germline VHL mutations in the Polish population; (3) the proportion of de novo mutations; and (4)
genotype-phenotype correlations in patients with a
deletion of the entire VHL gene.
\u2022 The coding region of the VHL gene was tested using
direct sequencing. Large deletions were analysed using
quantitative Southern blotting and/or multiplex PCR.
\u2022 (1) Germline VHL mutations were observed in 30/34
(88%) families. Mutations were not identified in 4/34
(12%) probands (five subjects/four families) with central
nervous system haemangioblastoma (cHAB) and/or
retinal angioma (rHAB). (2) Small intragenic mutations
were detected in 18/30 (60%) families; all were
located 3\u2032 of codon 53. Partial and complete gene
deletions were detected in 7/30 (23%) and 5/30
(17%) families, respectively. Five mutations were unique
to the Polish population. (3) Five of 30 (17%) VHL mutation positive probands were found to have no family
history of VHL. (4) Of 11 patients with complete
deletions, all developed cHAB, two presented with
rHAB, and none developed renal cell carcinoma (RCC).
\u2022 (1) Some patients with predominantly brain tumours
and/or retinal angioma do not have identifiable germline mutations in the VHL gene and may have somatic
mosaicism, or may be affected by mutations of different
nature or localisation than the mutations for which the
study assays are designed, or may be phenocopies of
the disease. An alternative explanation is the presence
of additional haemangioblastoma susceptibility genes.
(2) The main characteristics of germline VHL mutations
in the Polish population are similar to those reported in
other populations. However, we observed a higher proportion of patients with complete deletions (5/30,
17%), compared to those reported in other populations
(3-9%). There was no evidence of a founder effect for
complete deletions in our patients. (3) The apparent de
novo mutation rate is 3c20%. (4) A complete deletion of
the VHL gene results primarily in brain tumours. This
result may be useful in genetic counselling for subjects
with complete deletions