Preconceptional and prenatal screening for fragile X syndrome: experience with 40,000 tests.
OBJECTIVE
To determine the carrier frequency of fragile X syndrome, and the rate of expansion from premutation (PM) carrier to full mutation (FM) fetus.


METHODS
Results were analyzed on women with no family history of fragile X syndrome, or who were PM/FM carriers, who were tested between January 1994 and June 2004. PM was defined 55-199 repeats, FM above 200.


RESULTS
Out of 40 079 women screened, 5 FM and 255 PM carriers were detected. There was no significant difference in carrier frequency between those with versus those without family history of mental retardation or developmental abnormalities: 1 in 128 (28/3596) versus 1 in 157 (232/36 483). However, the median of repeats differed significantly: 58 and 66 repeats, respectively, (P < 0.0001). Invasive prenatal diagnosis was carried out in 370 pregnancies (7 FM and 363 PM). Thirty FM fetuses were detected. There was a lower expansion rate in cases without a family history: 10% (17/169 PMs) compared to 50% (11/22 PMs) in those with a history, but this could be accounted for by the difference in allele size.


CONCLUSIONS
There is now sufficient information on screening parameters and prenatal diagnosis of fragile X syndrome to offer testing to women of reproductive age.
Berkenstadt
Michal
M
Danek-Gertner Institute of Human Genetics, Sheba Medical Center, Tel-Hashomer, Israel. mberken@sheba.health.gov.il
Ries-Levavi
Liat
L
Cuckle
Howard
H
Peleg
Leah
L
Barkai
Gad
G
D001321:Autistic Disorder / Q000175:diagnosis / Q000235:genetics; D005260:Female; D005315:Fetal Diseases / Q000175:diagnosis / Q000235:genetics; D005600:Fragile X Syndrome / Q000175:diagnosis* / Q000235:genetics; D005787:Gene Frequency; D006580:Genetic Carrier Screening; D005820:Genetic Testing; D006801:Humans; D008607:Intellectual Disability / Q000175:diagnosis / Q000235:genetics; D008297:Male; D011247:Pregnancy; D019836:Preimplantation Diagnosis / Q000379:methods*; D011296:Prenatal Diagnosis / Q000379:methods*; D012189:Retrospective Studies