Fragile X syndrome

Fragile X syndrome (Fragile X chromosome syndrome, Martinův-Bell syndrome) is a disease that got its name from a specific chromosomal abnormality - fragility in the subterminal part of the long arms of the X chromosome (band Xq27.3 - FRAXA ), which occurs in the part of cells behind special cultivation conditions (low serum content, reduced folic acid content in the medium).

Pathogenesis In affected mentally retarded men, amplification of CCG / CGG trinucleotide sequences occurs in the promoter of the FMR1 gene, which lies in this region of the X chromosome. This mutation arises from a so-called premutation occurring in the mothers of affected men who have this amplification to a smaller extent (50-200 copies). Normal individuals also have some repeats of this sequence, but to a much lesser extent than individuals with the premutation (6–50 copies). The transformation of an unstable premutation into a full mutation (i.e., an increase in the length of the amplificate to more than 200 copies) occurs only during transmission by a woman, no elongation occurs when the element passes through spermiogenesis. Full mutation, i.e., an increase in trinucleotide repeats above 200 copies leads to methylation of this element, and since it is located in the gene promoter, gene transcription arrest and mental retardation and other clinical manifestations occur. It is assumed that amplification of the amplification can occur only in early embryogenesis (but is determined in gametogenesis ), which is evidenced by somatic heterogeneity in the length of the repeat, degree of methylation, and also the existence of individuals - mosaics full of mutation and premutation.

"New mutations", i.e. the emergence of a full mutation in the offspring of a person with a normal number of repeats, have not been described in this disease. The formation of a full mutation always happens by gradually increasing the element through premutation. The length of sequence repetition is correlated with the degree of mental retardation and with cytogenetic expression.

There is another fragile site (FRAXE) on the X chromosome associated with mild mental retardation.

Clinical signs mental retardation , long face rough features, big ears, macroorchidism. center|náhled|upright=1.6|Video v angličtině, definice, patogeneze, příznaky, komplikace, léčba.

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