Validation of a screening tool for the rapid and reliable detection of CGG trinucleotide repeat expansions in FMR1.
OBJECTIVE
Most individuals with intellectual disability and/or autism are tested for Fragile X syndrome at some point in their lifetime. Greater than 99% of individuals with Fragile X have an expanded CGG trinucleotide repeat motif in the promoter region of the FMR1 gene, and diagnostic testing involves determining the size of the CGG repeat as well as methylation status when an expansion is present.


RESULTS
Using a previously described triplet repeat-primed polymerase chain reaction, we have performed additional validation studies using two cohorts with previous diagnostic testing results available for comparison purposes. The first cohort (n=88) consisted of both males and females and had a high percentage of abnormal samples, while the second cohort (n=624) consisted of only females and was not enriched for expansion mutations. Data from each cohort were completely concordant with the results previously obtained during the course of diagnostic testing.


CONCLUSIONS
This study further demonstrates the utility of using laboratory-developed triplet repeat-primed FMR1 testing in a clinical setting.
Molecular Diagnostic Laboratory, Greenwood Genetic Center, Greenwood, South Carolina 29646, USA. mbasehore@ggc.org
Monica J
MJ
Basehore
Natalia M
NM
Marlowe
Julie R
JR
Jones
Deborah E
DE
Behlendorf
Thomas A
TA
Laver
Michael J
MJ
Friez
D000483:Alleles; D015331:Cohort Studies; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics*; D005600:Fragile X Syndrome / Q000175:diagnosis* / Q000235:genetics; D006801:Humans; D008607:Intellectual Disability; D008297:Male; D009154:Mutation; D016133:Polymerase Chain Reaction / Q000379:methods; D013997:Time Factors; D019680:Trinucleotide Repeat Expansion / Q000235:genetics*
D051860:Fragile X Messenger Ribonucleoprotein 1; C497683:FMR1 protein, human