Absence of FMR1 protein in two mentally retarded fragile X males without CGG repeat expansion
- Baylor College of Medicine, Houston, TX (United States)
- Univ. of Manitoba, Winnipeg (Canada)
Fragile X syndrome is characterized by absence of the product of the FMR1 gene due to an expansion and abnormal methylation of a CGG repeat located in exon 1. While the vast majority of fragile X patients demonstrate this common mutation, a small number of non-CGG mutations have been identified among patients exhibiting features of fragile X syndrome. Three patients with large deletions ablating all or a portion of FMR1 have been previously reported. A fourth patient has been described with a point mutation resulting in an Ile367 Asn substitution. While this last individual suggests that FMR1 is directly responsible for fragile X syndrome, the severe phenotype observed suggests a gain of function mutation. Our long-term goal is to understand both the normal function of the FMR1 gene product and the consequences of its absence. Using Western blot analysis of protein extracts prepared from transformed lymphoblastoid cell lines derived from individuals suspected of fragile X syndrome without CGG expansion, we have identified two fragile X males who display no FMR1 protein. In order to facilitate identification of small-scale mutations in these patients, primers have been designed which allow amplification of each exon of the FMR1 gene along with their intron boundaries. Exons 2 through 17 of FMR1 have been analyzed by amplification of patient genomic DNA using these primers. Each patient shows normal length amplification product from each exon as assayed by agarose gel electrophoresis, suggesting the absence of insertions, deletions, or other rearrangements. Sequence analysis of exons 8, 9, 10, 11, and 12 has shown no alteration from the normal FMR1 sequence. Current analysis has focused on the use of mutation detection electrophoresis (MDE) in order to identify candidate exons for mutations. RT-PCR analysis is also under way to determine if FMR1 mRNA is present and to offer an alternative approach to mutation detection.
- OSTI ID:
- 134253
- Report Number(s):
- CONF-941009-; ISSN 0002-9297; TRN: 95:005313-0989
- Journal Information:
- American Journal of Human Genetics, Vol. 55, Issue Suppl.3; Conference: 44. annual meeting of the American Society of Human Genetics, Montreal (Canada), 18-22 Oct 1994; Other Information: PBD: Sep 1994
- Country of Publication:
- United States
- Language:
- English
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