Extreme variation between blood and fibroblast DNA patterns in mosaic fragile X males
- New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY (United States); and others
The fragile X mutation is the expansion of a CGG repeat in the 5{prime} untranslated region of the FMR-1 gene to > 200 repeats. This expansion to the {open_quotes}full mutation{close_quotes} probably occurs during early embryogenesis in individuals who inherit a {open_quotes}premutation{close_quotes} allele containing >50 and <200 repeats. Analysis of blood samples from a series of 148 fragile X males showed that 40% were {open_quotes}mosaics{close_quotes} who carried a mixture of premutation and full mutation alleles. The proportion of the premutation allele varied widely which suggested that there may have been differences in the way the repeat expanded during development. We examined a subset of these affected {open_quotes}mosaic{close_quotes} males who exhibited very different mosaic DNA patterns. Southern blot analysis showed that these males had a range of approximately 10 to 80% premutation allele in their blood DNA. In fibroblast DNA, however, the premutation allele was present at less than 10% in all of these affected males. Since erythrocyte stem cell precursors appear to be established from a yolk sac lineage,earlier in development compared to skin fibroblasts, we hypothesize that this difference in the extent of mosaicism may reflect variation in the progression of the CGG expansion during development. The differences in the proportion of mosaic alleles in different tissues may also help explain the weak correlation between the mosaic DNA patterns of blood samples from mosaic males and their degree of mental retardation.
- OSTI ID:
- 134198
- Report Number(s):
- CONF-941009--
- Journal Information:
- American Journal of Human Genetics, Journal Name: American Journal of Human Genetics Journal Issue: Suppl.3 Vol. 55; ISSN AJHGAG; ISSN 0002-9297
- Country of Publication:
- United States
- Language:
- English
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