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Analysis of the LMNA gene and the SH3TC2 gene among Czech patients with hereditary neuropathy Charcot-Marie-Tooth type 1 and 2
Laššuthová, Petra ; Seeman, Pavel (advisor) ; Martásek, Pavel (referee) ; Fajkusová, Lenka (referee)
My PhD thesis can be devided into two parts: 1. Hereditary motor-sensory neuropathies (HMSN) 2. Selected muscle disorders The main emphasis was on the first part - hereditary motor and sensory neuropathies. Research was focused on autosomal recessive forms - demyelinating type CMT4C and axonal type CMT2B1. Most of the results obtained are related to these disorders. Data, which were obtained, are unique and were published in international journals with impact factor. Results obtained from CMT4C study are accepted for publication in Clinical Genetics. Results obtained in LMNA study (CMT2B1) were published in Journal of Human Genetics. The author performed and validated these new methods and original results, which are due to be used in genetic molecular testing of patients with hereditary neuropathies and muscle disorders: 1. Sequencing of all coding exons of the SH3TC2 gene. First mutations in the SH3TC2 gene in Czech HMSN I patients were found. 2. The prevalent mutation among Czech CMT4C patients was proven to be p.Arg954Stop. 3. Real-time PCR assay targeted at detection of the prevalent mutation p.Arg954Stop in the SH3TC2 gene was validated and is now used in our lab on a daily basis as a quick and efficient screening. 4. Molecular genetic testing of the SH3TC2 gene was introduced into the routine...
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Molecular genetic analysis of the fragile X syndrome and myotonic dystrophy
Mušová, Zuzana ; Sedláček, Zdeněk (advisor) ; Fajkusová, Lenka (referee) ; Maxová, Alica (referee)
More than 20 human hereditary diseases have been linked to expansions of unstable simple nucleotide repeats. These disorders include several clinically heterogeneous neurological diseases such as the fragile X syndrome (FXS), Friedreich's ataxia (FRDA1), Huntington's disease (HD), multiple types of spinocerebellar ataxias (SCA), and myotonic dystrophy type 1 (DM1). The phenotype of these disorders shows wide variability ranging from mild symptoms with late onset to severe congenital forms. The pathogenic mechanism of these expansions depends mainly on the type, localization and length of the repeat. Expansions of tracts of CAG triplets in coding regions cause polyglutamine disorders with abnormal protein function. Expanded non-coding repeats can silence gene expression or produce toxic RNAs which can be engaged in abnormal interactions with RNA-binding proteins [reviewed in 1]. The fragile X syndrome is one of the most common causes of inherited mental retardation with estimated frequency of 1 in 4000-9000 males and 1 in 7000-15000 females [2]. The disorder is associated with the expansion of a polymorphic CGG repeat in the 5' untranslated region of the FMR1 gene in Xq27.3 [3-6]. Affected males with full mutations (over 200 CGG repeats) have mental impairment with dysmorphic features (elongated face,...
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