Aim: To determine whether four potential genetic factors (polymorphisms in genes for alpha‐adducin, beta‐adducin, the G‐protein beta‐3 subunit and nitric oxide synthase) are important for the ...development of essential hypertension (EH) in Slovenian children and young adults with EH. Methods: Both a nuclear families approach and case‐control study have been performed. Genotyping of common polymorphisms in these genes using polymerase chain reaction was carried out in 104 nuclear families (an affected child, both parents) and in 200 control patients. Results: Using the transmission disequilibrium test, no statistically significant differences were found between the frequencies of transmitted and non‐transmitted alleles in nuclear families for all four investigated polymorphisms. In addition, the distributions of genotypes and alleles for the four polymorphisms did not differ significantly between our children and 200 healthy control patients. The allele frequencies of all polymorphisms were concordant with those observed in some other Caucasian populations.
Conclusion: We found no association between the investigated gene variants and EH, so we conclude that they do not confer a significantly increased risk of the development of EH in the Slovenian population of hypertensive children.
We report a 13-month-old male infant with an apparently normal karyotype, severe growth and developmental delay, ichthyosis, hypogonadism, limb shortness, hypoplasia of the corpus callosum and a ...round, flat face and thin upper lip as a consequence of a subtelomeric del/dup event of the X chromosome. The recombinant X chromosome (rec(X)), derived from crossing-over within the inversion, was identified in a family, in which the mother is a carrier of pericentric inversion of one X chromosome and pericentric inversion of the heterochromatic region of chromosome 9. The inv(X) chromosome was also analysed in her sister and daughter. The rec(X) had a duplication of the segment Xq27.3-->Xqter and deletion of the Xp22.31-->Xpter and was interpreted as Xqter-Xq27.3::Xp22.31-Xqter. The rec (X) was characterised by FISH using a number of BAC probes. There are only three published reports of chromosome rearrangements resulting in a similar subtelomeric duplication of Xq in males. The proband's phenotype corresponds to descriptions of contiguous gene syndromes due to deletion of the STS, SHOX, ARSE and KAL genes. Despite the loss of the ARSE gene there was no evidence of chondrodysplasia punctata. Additional conditions associated with duplication of the Xq28 segment, such as severe growth retardation and developmental delay, a peculiar head shape, atrophy of the cerebral hemispheres and hypoplasia of the cerebellum and corpus callosum, were observed.
Fluorescent in situ hybridisation techniques using subtelomeric DNA probes are essential tools for detection of such complex submicroscopic chromosomal rearrangements as the dup/del event of the X chromosome described in our patient.
Hypoxanthine phosphoribosyltransferase (HPRT) deficiency is an inherited disorder. Complete deficiency of HPRT activity is phenotypically expressed as the devastating Lesch-Nyhan syndrome. Partial ...HPRT deficiency usually causes hyperuricemia, precocious gout, and uric acid nephrolithiasis. We describe an 18-year follow-up of a 5-year old boy with partial HPRT deficiency and report a novel mutation in his HPRT gene. He presented with overproduction of uric acid and passage of uric acid renal stones, and without gout or neurological and behavioral abnormalities. Treatment with allopurinol, adequate hydration, urinary alkalization, and a low-purine diet was started. No subsequent nephrolithiasis has occurred. After 18-year of this therapy his physical and neuropsychological status were normal, merely his glomerular filtration rate (GFR, normal 97-137 mL min(-1)/1.73 m(2)) fell from normal to 65.1 mL min(-1). The most likely cause of initial renal impairment in our patient is uric and/or xanthine crystalluria. A missense and transition mutation 169A>G (57ATG>GTG, 57met>val) in exon 3 of the patient's HPRT gene was identified and the mother was the carrier of the mutation. As far as we are aware, the identified mutation has not previously been reported. We named the mutant HPRT Maribor.
Partial trisomy of the long arm of chromosome 10 is a well-defined but rare syndrome. Clinical features of this chromosomopathy are a distinctive dysmorphic appearance, developmental delay, growth ...retardation, and in some cases, abnormalities of the extremities and renal, cardiac and ocular anomalies. This report describes a neonate with symmetric growth retardation and multiple dysmorphic features, in whom chromosomal analysis revealed a partial trisomy of chromosome 10q with a monosomy of the 13q34 region. The phenotype shares many common features with previously published cases. In addition to the typical features, our case also shows renal hypoplasia with early renal insufficiency and some genital anomalies.
A family history of cardiovascular disease predicts cardiovascular risk in the next generation, which is either the result of inherited traits or certain living habits in some families. The aim of ...our study was to evaluate both variables and particularly the role of one of the possible genetic risk factors - angiotensin-converting enzyme (ACE) gene polymorphism. History and anthropometric and biochemical parameters, ACE gene polymorphism and carotid wall thickness - intima media thickness (IMT) were studied in two groups of children: in children whose parents had a stroke before the age of 45 years and in children without a positive family history. The preliminary results of the present study failed to confirm our hypothesis that ACE gene polymorphism is a cardiovascular risk factor in children of parents with premature stroke.
The C825T polymorphism in the GNB3 gene encoding a β3 subunit from heterotrimeric G-proteins correlates strongly with the variation in activity of the G-proteins. It has so far been associated with a ...variety of medical conditions, but has not been tested for association with vesico-ureteric reflux (VUR). Primary VUR is a condition of genetic origin that appears to be inherited in an autosomal dominant mode, but with reduced penetrance. The constitutional change in G-protein-mediated cell signaling associated with the C825T polymorphism might be one of the factors that participate in the development of VUR by modifying the effect of still unknown mutated gene(s). A significant difference in genotype frequencies (
χ
2 = 7.38,
P = 0.025, df = 2) was observed between patients with primary VUR (33 CC homozygotes, 40 CT heterozygotes, 12 TT homozygotes) and healthy controls with no medical record of reflux (114 CC homozygotes, 88 CT heterozygotes, 18 TT homozygotes). This result suggests that the C825T polymorphism of the GNB3 gene might be associated with the development of VUR.
The C825T polymorphism in the GNB3 gene encoding a beta3 subunit from heterotrimeric G-proteins correlates strongly with the variation in activity of the G-proteins. It has so far been associated ...with a variety of medical conditions, but has not been tested for association with vesico-ureteric reflux (VUR). Primary VUR is a condition of genetic origin that appears to be inherited in an autosomal dominant mode, but with reduced penetrance. The constitutional change in G-protein-mediated cell signaling associated with the C825T polymorphism might be one of the factors that participate in the development of VUR by modifying the effect of still unknown mutated gene(s). A significant difference in genotype frequencies (chi(2) = 7.38, P = 0.025, df = 2) was observed between patients with primary VUR (33 CC homozygotes, 40 CT heterozygotes, 12 TT homozygotes) and healthy controls with no medical record of reflux (114 CC homozygotes, 88 CT heterozygotes, 18 TT homozygotes). This result suggests that the C825T polymorphism of the GNB3 gene might be associated with the development of VUR.
