Molecular heterogeneity of the fragile X syndrome - PubMed (original) (raw)

Molecular heterogeneity of the fragile X syndrome

Y Nakahori et al. Nucleic Acids Res. 1991.

Free PMC article

Abstract

The fragile X syndrome is an X-linked disorder which has been shown to be associated with the length variation of a DNA fragment containing a CGG trinucleotide repeat element at or close to the fragile site. Phenotypically normal carriers of the disorder generally have a smaller length variation than affected individuals. We have cloned the region in cosmids and defined the area containing the amplified sequence. We have used probes from the region to analyse the mutation in families. We show that the mutation evolves in different ways in different individuals of the same family. In addition we show that not all fragile X positive individuals show this amplification of DNA sequence even though they show expression of the fragile site at levels greater than 25%. One patient has alterations in the region adjacent to the CGG repeat elements. Three patients in fragile X families have the normal fragment with amplification in a small population of their cells. These observations indicate that there is molecular heterogeneity in the fragile X syndrome and that the DNA fragment length variation is not the only sequence responsible for the expression of the fragile site or the disease phenotype.

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References

1. 1. Nucleic Acids Res. 1991 Jun 25;19(12):3283-8 - PubMed
2. 1. Genomics. 1991 May;10(1):243-9 - PubMed
3. 1. Science. 1977 Jul 15;197(4300):265-6 - PubMed
4. 1. Anal Biochem. 1983 Jul 1;132(1):6-13 - PubMed
5. 1. Ann Hum Genet. 1984 Jan;48(Pt 1):21-37 - PubMed

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