Abstract
Fragile X Syndrome is caused by the expansion of an unstable CGG-repeat tract in the 5′-UTR of the FMR1 gene, which generally results in transcriptional silencing and consequent absence of the FMR1 protein. To date, the smallest premutation allele reported to expand to a full mutation allele in a single generation is 59 CGG repeats. Here, we report a single-generation expansion to a full mutation allele (male with ∼538 CCG repeats) from a mother who is a carrier of a premutation allele of 56 CGG repeats. Furthermore, the maternal grandfather was a carrier of a gray (or intermediate)-zone allele (45 to 54 repeats) of 52 CGG repeats. Thus, in this family, a gray-zone allele expanded to the full mutation range in two generations. Interestingly, the two AGG interruptions present in the grandfather's allele were absent in the mother's premutation allele. These observations underscore the need to consider carriers of alleles of greater than 55 CGG repeats as being at risk for transmission of a full mutation allele in a single generation, and those with even smaller alleles in the gray zone as being at risk of having grandchildren with full mutation alleles.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 306-310 |
| Number of pages | 5 |
| Journal | Journal of Molecular Diagnostics |
| Volume | 11 |
| Issue number | 4 |
| DOIs | |
| State | Published - Jul 2009 |
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ASJC Scopus subject areas
- Molecular Medicine
- Pathology and Forensic Medicine
Cite this
Expansion of an FMR1 grey-zone allele to a full mutation in two generations. / Fernandez-Carvajal, Isabel; Posadas, Blanca Lopez; Pan, Ruiqin; Raske, Christopher; Hagerman, Paul J; Tassone, Flora.
In: Journal of Molecular Diagnostics, Vol. 11, No. 4, 07.2009, p. 306-310.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Expansion of an FMR1 grey-zone allele to a full mutation in two generations
AU - Fernandez-Carvajal, Isabel
AU - Posadas, Blanca Lopez
AU - Pan, Ruiqin
AU - Raske, Christopher
AU - Hagerman, Paul J
AU - Tassone, Flora
PY - 2009/7
Y1 - 2009/7
N2 - Fragile X Syndrome is caused by the expansion of an unstable CGG-repeat tract in the 5′-UTR of the FMR1 gene, which generally results in transcriptional silencing and consequent absence of the FMR1 protein. To date, the smallest premutation allele reported to expand to a full mutation allele in a single generation is 59 CGG repeats. Here, we report a single-generation expansion to a full mutation allele (male with ∼538 CCG repeats) from a mother who is a carrier of a premutation allele of 56 CGG repeats. Furthermore, the maternal grandfather was a carrier of a gray (or intermediate)-zone allele (45 to 54 repeats) of 52 CGG repeats. Thus, in this family, a gray-zone allele expanded to the full mutation range in two generations. Interestingly, the two AGG interruptions present in the grandfather's allele were absent in the mother's premutation allele. These observations underscore the need to consider carriers of alleles of greater than 55 CGG repeats as being at risk for transmission of a full mutation allele in a single generation, and those with even smaller alleles in the gray zone as being at risk of having grandchildren with full mutation alleles.
AB - Fragile X Syndrome is caused by the expansion of an unstable CGG-repeat tract in the 5′-UTR of the FMR1 gene, which generally results in transcriptional silencing and consequent absence of the FMR1 protein. To date, the smallest premutation allele reported to expand to a full mutation allele in a single generation is 59 CGG repeats. Here, we report a single-generation expansion to a full mutation allele (male with ∼538 CCG repeats) from a mother who is a carrier of a premutation allele of 56 CGG repeats. Furthermore, the maternal grandfather was a carrier of a gray (or intermediate)-zone allele (45 to 54 repeats) of 52 CGG repeats. Thus, in this family, a gray-zone allele expanded to the full mutation range in two generations. Interestingly, the two AGG interruptions present in the grandfather's allele were absent in the mother's premutation allele. These observations underscore the need to consider carriers of alleles of greater than 55 CGG repeats as being at risk for transmission of a full mutation allele in a single generation, and those with even smaller alleles in the gray zone as being at risk of having grandchildren with full mutation alleles.
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UR - http://www.scopus.com/inward/citedby.url?scp=69249093477&partnerID=8YFLogxK
U2 - 10.2353/jmoldx.2009.080174
DO - 10.2353/jmoldx.2009.080174
M3 - Article
C2 - 19525339
AN - SCOPUS:69249093477
VL - 11
SP - 306
EP - 310
JO - Journal of Molecular Diagnostics
JF - Journal of Molecular Diagnostics
SN - 1525-1578
IS - 4
ER -