Peculiar fragile X {open_quotes}mosaics{close_quotes} suggest deletion from full mutations as a mechanism for generating {open_quotes}mosaic{close_quotes} cases
- Laval Univ., Quebec (Canada)
- Univ. of Sherbrooke (Canada); and others
We report four cases of fragile X males with a {open_quotes}mosaic{close_quotes} pattern as detected by Southern blot analysis with probe StB12.3. These four {open_quotes}mosaics{close_quotes} are peculiar as full mutations are observed without premutations but rather associated with an EcoRI-EagI fragment of normal or reduced size. We have sequenced the fragment of reduced size and determined that the CGG repeats were missing as part of a 99 bp deletion with respect of the published FMR-1 gene sequence. Otherwise, the three other cases showed, in association with full mutations, a fragment of normal size including the CGG repeats. These cases did not show any premutation in association to their full mutations but rather normal or subnormal fragments where part or all of the CGG repeats were deleted at some time, most probably from a full mutation since premutations are known to be much more stable somatically. These cases raise the question whether usual {open_quotes}mosaic{close_quotes} cases (full + premature) are generated from the absence of postzygotic expansion of a premutation transmitted as such by the carrier mother or from a deletion of a full mutation during their period of somatic instability. Furthermore, these cases of {open_quotes}normal + full mosaics{close_quotes}, even if rare, challenge the usual DNA-based diagnostic means as the presence of a normal-sized fragment in part of the cells may be falsely interpreted as a normal genotype with catastrophic consequences in a context of prenatal diagnosis. This suggests again that Southern blotting with overexposure may be the preferred diagnostic method.
- OSTI ID:
- 134311
- 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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