Molekulárně genetická analýza syndromu fragilního chromozomu X a myotonické dystrofie

• Main Author: Mušová, Zuzana
• Other Authors: Sedláček, Zdeněk
• Format: Doctoral Thesis
• Language: Czech
• Published: 2010
• Online Access: http://www.nusl.cz/ntk/nusl-278026

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,...