Biomedical subjects

Z Pribilincova

Publications and source records attributed to Z Pribilincova.

3 recordsLinked to original sources

PubMed2005

Mutational spectrum of steroid 21-hydroxylase and the genotype-phenotype association in Middle European patients with congenital adrenal hyperplasia.

OBJECTIVE: To analyze the mutational spectrum of steroid 21-hydroxylase (CYP21) and the genotype- phenotype correlation in patients with congenital adrenal hyperplasia (CAH) registered in the Middle European Society for Pediatric Endocrinology CAH database, and to design a reliable and rational approach for CYP21 mutation detection in Middle European populations. DESIGN AND METHODS: Molecular analysis of the CYP21 gene was performed in 432 CAH patients and 298 family members. Low-resolution genotyping was performed to detect the eight most common point mutations. High-resolution genotyping, including Southern blotting and sequencing was performed to detect CYP21 gene deletions, conversions, point mutations or other sequence changes. RESULTS: CYP21 gene deletion and In2 and Ile172Asn mutation accounted for 72.7% of the affected alleles in the whole study group. A good genotype-phenotype correlation was observed, with the exception of Ile172Asn and Pro30Leu mutations. In 37% of patients low resolution genotyping could not identify the causative mutation or distinguish homozygosity from hemizygosity. Using high-resolution genotyping, the causative mutations could be identified in 341 out of 348 analyzed patients. A novel mutation Gln315Stop was found in one simple virilising CAH (SV-CAH) patient from Austria. In the remaining seven patients polymorphisms were identified as the leading sequence alteration. The presence of elevated basal and ACTH-stimulated 17-hydroxyprogesterone, premature pubarche, advanced bone age and clitoral hypertrophy directly implicated Asn493Ser polymorphism in the manifestation of nonclassical- (NC) and even SV-CAH. CONCLUSIONS: By genotyping for the most common point mutations, CYP21 gene deletion/conversion and the 8 bp deletion in exon 3, it should be possible to identify the mutation in 94-99% of the diseased alleles in any investigated Middle European population. In patients with a mild form of the disease and no detectable mutation CYP21 gene polymorphisms should be considered as a plausible disease-causing mutation.

Adrenal Hyperplasia, Congenital↗

PubMed2002

Congenital adrenal hyperplasia: lessons from a multinational study.

A study group of paediatric endocrinologists was established in Austria, Czech Republic, Hungary, Slovenia and Slovakia in order to investigate various aspects in children with congenital adrenal hyperplasia (CAH). Five hundred and ninety-eight patients with CAH who were diagnosed between 1969 and 1998 were included in order to analyze the following questions. Epidemiological data: There were significantly fewer males (43%) than females (57%), and the percentage of males did not increase during the observation period. Salt wasters (SW) totalled 64.7%, whereas 35.3% had simple virilizing (SV) CAH. Diagnosis was established significantly later in boys than in girls (median of 26 vs. 13 days for SW, p < 0.0001; 1,817 vs. 1,010 days for SV, p < 0.03). Mortality in the general population was significantly lower than in CAH siblings (1.8% vs. 7.0%, p < 0.0001) or in SW children (2.2% vs. 11.3%, p < 0.0001). According to our calculation with the present clinical diagnostic criteria in Central Europe, from 40 expected CAH patients/year, 2-2.5 SW, and one female and four male SV patients will not be diagnosed. Auxological data: Growth data from 341 patients were analyzed retrospectively. Percentiles were constructed in a longitudinal/cross-sectional study and pubertal growth was described in a longitudinal analysis. Growth of SW patients was impaired in early childhood (0-3 years), but followed a normal course until puberty. In contrast, SV children had a normal growth pattern during early childhood, but were above the standard thereafter. The pubertal growth spurt was of normal magnitude in boys and girls, but started too early. Final height was reduced compared with both standard and target heights. There was no correlation between final height and age of starting treatment or the year of birth. Bone age was accelerated in both CAH types, but more so in SV patients. Molecular genetics: Three hundred and fifty-six patients were investigated for 11-14 of the most frequent mutations by direct allele-specific polymerase chain reaction (PCR) and/or PCR followed by sequence-specific oligonucleotide, single strand chain polymorphism and restriction fragment length polymorphism. In the group as a whole, we most frequently found the Intron 2 splice mutation (30.8%) or a deletion/conversion (28.5%). The Intron 2 mutation was most frequent in the Hungarian population, whereas deletions/conversions were found more frequently in Slovenians. The other mutations had a similar distribution to those seen in other populations. Genotype-phenotype correlation confirms previous reports.

Adolescent↗

PubMed2000

PCR based diagnosis of 21-hydroxylase gene defects in Slovak patients with congenital adrenal hyperplasia.

OBJECTIVE: To analyse 21-hydroxylase gene for 8 most common mutations in patients with salt-wasting type of congenital adrenal hyperplasia. METHODS: Allele specific PCR performed on 8 salt-wasting CAH patients and their 23 healthy relatives. RESULTS: Two patients were homozygous for 8 bp deletion in exon 3, while 6 patients were homozygous for intron 2 splice mutation. Mutant allele for splice mutation was found also in both parents of patients with this type of mutation. CONCLUSIONS: These preliminary results show that only two mutations, 8 bp deletion in exon 3 and splice mutation in intron 2, were present in this group of Slovak patients with salt-wasting type of congenital adrenal hyperplasia.

Adolescent↗