Molecular testing for Fragile X Syndrome: lessons learned from 119,232 tests performed in a clinical laboratory.
OBJECTIVE
To examine the data from over 119,000 Fragile X Syndrome tests and 307 prenatal tests to detect unsuspected findings and obtain clinical data when indicated to optimize genetic counseling.


METHODS
A proprietary database containing 119,232 consecutive postnatal and 307 prenatal FXS tests performed between November 2, 1992 and June 1, 2006 was queried.


RESULTS
The distribution of normal FMR1 alleles was a bimodal distribution with a major peak at 30 repeats and a minor peak at 21 repeats. Of 59,707 tests performed for males, 1.4% had a fully expanded and methylated FMR1 allele. Of 59,525 tests performed for females, 0.61% had an affected FMR1 allele, and 1.7% had a premutation FMR1 allele for a total carrier frequency of 1.3%. When fetuses inherited an expanded maternal allele, the risk of expansion to a full affected allele was 0%, 5%, 30% and 100% for allele sizes of <50, 50-75, 76-100 and >100 repeats, respectively.


CONCLUSIONS
These figures can be used for genetic counseling of patients presenting for carrier detection and prenatal diagnosis for Fragile X Syndrome.
Strom
Charles M
CM
Nichols Institute, Quest Diagnostics, 33608 Ortega Highway, San Juan Capistrano, California 92690, USA. charles.m.strom@questdiagnostics.com
Crossley
Beryl
B
Redman
Joy B
JB
Buller
Arlene
A
Quan
Franklin
F
Peng
Mei
M
McGinnis
Matthew
M
Fenwick
Raymond G
RG
Sun
Weimin
W
D000328:Adult; D002648:Child; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics*; D005600:Fragile X Syndrome / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics; D005787:Gene Frequency; D005817:Genetic Counseling; D005820:Genetic Testing; D006579:Heterozygote; D006801:Humans; D007753:Laboratories; D008297:Male; D011296:Prenatal Diagnosis; D019680:Trinucleotide Repeat Expansion
D051860:Fragile X Messenger Ribonucleoprotein 1; C497683:FMR1 protein, human