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Molecular genetic analysis of chromosomal region 8q24 in patients with trichorhinophalangeal syndrome or isolated exostosis
Klugerová, Michaela ; Šolc, Roman (advisor) ; Křepelová, Anna (referee)
Trichorhinophalangeal syndrome is a malformation syndrome characterized by craniofacial and skeletal abnormalities and is inherited in an autosomal dominant manner. We distinguish free subtypes on clinical and molecular level - TRPS I, TRPS II, TRPS III. All TRPS patients have sparse hair, a pear-shaped nose, a long flat philtrum, a thin upper lip and protruding ears. Skeletal abnormalities include cone-shaped epiphyses at the phalanges, hip malformations and short stature are present. The subgroups TRPS I and TRPS III are result of the mutated TRPS1 gene, which is maped into the 8q24 region. This gene is situated proximal of the EXT1 gene, both genes are affected in a subgroup of patients with TRPS II. These patients suffer more from multiple (cartilaginous) exostoses and mental retardation. In this work we performed molecular genetic analysis of a sample of 16 patients, 8 probands showed a TRPS phenotype and 8 probands had only isolated exostoses. The peripheral venous blood of patients was used to gain purified DNA, which was subsequently used to investigate the chromosome 8q24 region using MLPA ("multiplex ligation-dependent probe amplification"). This analysis revealed a deletion in 1 TRPS patient and 1 patient with exostoses. Sequencing of the TRPS1 gene coding exons in remaining 7 TRPS...
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Genetic factors affecting course of selected forms of nephrotic syndrome
Šafaříková, Markéta ; Štekrová, Jitka (advisor) ; Král, Jiří (referee)
Nephrotic syndrome (NS) is characterized by proteinuria, hypalbuminemia and edemas. It occurs during first and second glomerulopathies. This disease can be divided into two groups: primary (idiopathic) and secondary. The heredity of the familial nephrotic syndrome is autosomal dominant and autosomal recessive. There are four most important genes that condition the formation of hereditary nephrotic syndrome in adult patienst. These genes are ACTN4, CD2AP, NPHS2 and TRPC6. The gene ACTN4, which encodes protein α-actinin 4, is responsible for the autosomal dominant form of focal segmental glomerulosclerosis (FSGS). FSGS is included in first glomerulopathies. α-Actinin 4 was also researched for some types of carcinomas. There was performed the mutational analysis of the gene ACTN4 on the set of 48 patients with nephrotic syndrome in this diploma thesis. High resolution melting (HRM) analysis and sequencing selected samples were used during this mutation detection. During this process many published and unpublished SNPs and one unpublished candidate mutation that could have causal associations with FSGS were found.
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