Novel mutations of the APC gene and genetic consequences of splicing mutations in the Czech FAP families.

Familial adenomatous polyposis (FAP) is an autosomal dominant syndrome with almost 100 % risk of colorectal cancer. The typical FAP is characterized by hundreds to thousands of colorectal adenomatous polyps and by extracolonic manifestations, later onset and lower number of polyps in colon is characteristic of an attenuated form (AFAP). We analyzed the APC gene for germline mutations in 90 FAP/AFAP patients.

Application of the new insertion-deletion polymorphism kit for forensic identification and parentage testing on the Czech population.

Insertion-deletion polymorphisms (INDELs) are diallelic markers derived from a single mutation event. Their low mutation frequency makes them suitable for forensic and parentage testing. The examination of INDELs thus combines advantages of both short tandem repeats (STR) and single nucleotide polymorphisms (SNP).

Cryptic chromosomal rearrangements in children with idiopathic mental retardation in the Czech population.

Aims: The aim of our study was to scan for cryptic rearrangements using the multiplex ligation probe amplification method in a cohort of 64 probands with mental retardation or developmental delays in combination with at least one of the following symptoms: hypotonia after birth, congenital anomalies, or face dysmorphisms; but without a positive cytogenetic finding. The study contributes to the knowledge of microdeletion syndromes and helps disclose their natural phenotypic variability.

Results: In total, 10 positives (16%) were detected, particularly 3 duplications (Xpter-p22.

New mutations in the PKD1 gene in Czech population with autosomal dominant polycystic kidney disease.

Background: Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary renal disease. The disease is caused by mutations of the PKD1 (affecting roughly 85% of ADPKD patients) and PKD2 (affecting roughly 14% of ADPKD patients) genes, although in several ADPKD families, the PKD1 and/or PKD2 linkage was not found. Mutation analysis of the PKD1 gene is complicated by the presence of highly homologous genomic duplications of the first two thirds of the gene.

Novel APC mutations in Czech and Slovak FAP families: clinical and genetic aspects.

Background: Germline mutations in the adenomatous polyposis gene (APC) result in familial adenomatous polyposis (FAP). FAP is an autosomal dominantly inherited disorder predisposing to colorectal cancer. Typical FAP is characterized by hundreds to thousands of colorectal adenomatous polyps and by several extracolonic manifestations.

Detection of variability in apo(a) gene transcription regulatory sequences using the DGGE method.

Background: Increased lipoprotein(a), Lp(a), concentration is an independent risk factor for premature atherosclerosis. Apolipoprotein(a), apo(a), determines properties of the lipoprotein and its production rate is the limiting step in Lp(a) particle formation.

Methods: Subjects covering the whole range of Lp(a) concentration were separated into quintiles.

The S18Y polymorphism in the UCHL1 gene is a genetic modifier in Huntington's disease.

An expanded polyglutamine stretch in the huntingtin protein has been identified as the pathogenetic cause of Huntington's disease (HD). Although the length of the expanded polyglutamine repeat is inversely correlated with the age-at-onset, additional genetic factors are thought to modify the variance in the disease onset. As linkage analysis suggested a modifier locus on chromosome 4p, we investigated the functional relevance of S18Y polymorphism of the ubiquitin carboxy-terminal hydrolase L1 in 946 Caucasian HD patients.

PKD2 mutations in a Czech population with autosomal dominant polycystic kidney disease.

Background: Autosomal dominant polycystic kidney disease (ADPKD) is genetically heterogeneous and caused by mutations in at least three different loci. Based on linkage analysis, mutations in the PKD2 gene are responsible for approximately 15% of the cases. PKD2-linked ADPKD is supposed to be a milder form of the disease, its mean age of end-stage renal failure (ESRF) approximately 20 years later than PKD1.