Full mutation

Fragile X families exhibit two types of FMR1 gene mutation. The repeat expansion of more than 230 copies with subsequent methylation of the CpG island is referred to as a full mutation. All males and about half of the females who carry full mutations have mental retardation. Mosaic males with full mutations are almost always affected to the same extent as fully affected males, while mosaic females vary in... 

Male fetuses with 50 to 230 copies of the repeat should be asymptomatic, whereas those with more than 230 copies will have fragile X syndrome. Female fetuses with 50 to 230 copies also will be asymptomatic however, it is difficult to predict the extent of mental retardation in female fetuses with more than 230 copies of the repeat. Although hypermethylation of the CpG island is a poor prognostic indicator, it is not always present in DNA extracted from chorionic villus samples (Sutherland et al., 1991). Empiric data showing that female carriers with full mutations have nearly a 50% risk of mental impairment should be considered reliable. 

Fragile X syndrome Xq27.3 CGG Maternal 6-50 Premutation 50-230 Full mutation 230-2000 FMR1... 

Fragile XE syndrome Xq28 CGG (-) 6-25 Premutation 25-200 Full mutation >200 FMR2... 

Huntington disease 4pl6.3 CAG Paternal 9-37 Premutation 30-38 Full mutation 37-121 Huntingtin... 

Myotonic dystrophy 19ql3.3 CTG Maternal 5-35 Premutation 50-80 Full mutation 80-2000 Myotonin protein kinase... 

Both the aunt (II-6) and the sister (III-3) of the patients had fragile X expression and apparent full mutation. Why was the... 

Figure 40-7 Schematic representation of the CGG repeat in exon I of FAIR/ and associated alleles. A CGG-repeat number less than or equal to 45 Is normal. A CGG-repeat number of 46 to 54 is in the gray zone and has been reported to expand to a full mutation in some families. A CGG-repeat number of 55 to 200 is considered a premutation allele and is prone to expansion to a full mutation during female meiosis. A CGG-repeat number in excess of 200 is considered a full mutation and is diagnostic of fragile X syndrome.

Heitz D, Devus D, Imbert G, Kretz C, Mandel JL. Inheritance of the fragile X syndrome size of the fragile X premutation is a major determinant of the transition to full mutation. J Med Genet 1992 29 794-801. 

Moutou C, Vincent MC, BiancalanaV, Mandel JL. Transition from premutation to full mutation m... 

Molecular basis of disease Mutation resulting in an increased number of CGG repeats on the X chromosome. When the nnmber of repeats reaches a critical size, it can be methylated and inactivated resulting in the disorder. Individuals who carry 50 to 199 repeats are phenotypically normal and carry a premutation. If repeats exceed 200, the patient has a full mutation and if methylation occurs, he or she will be affected. 

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