RT Journal Article
SR Electronic
T1 Prenatal diagnosis of the fragile X syndrome: loss of mutation owing to a double recombinant or gene conversion event at the FMR1 locus.
JF Journal of Medical Genetics
JO J Med Genet
FD BMJ Publishing Group Ltd
SP 924
OP 926
DO 10.1136/jmg.34.11.924
VO 34
IS 11
A1 M Losekoot
A1 E Hoogendoorn
A1 R Olmer
A1 C C Jansen
A1 J C Oosterwijk
A1 A M van den Ouweland
A1 D J Halley
A1 S T Warren
A1 R Willemsen
A1 B A Oostra
A1 E Bakker
YR 1997
UL http://jmg.bmj.com/content/34/11/924.abstract
AB The fragile X syndrome, an X linked mental retardation syndrome, is caused by an expanded CGG repeat in the first exon of the FMR1 gene. In patients with an expanded repeat the FMR1 promoter is methylated and, consequently, the gene is silenced and no FMR1 protein (FMRP) is produced, thus leading to the clinical phenotype. Here we describe a prenatal diagnosis performed in a female from a fragile X family carrying a large premutation. In chorionic villus DNA of the male fetus the normal maternal CGG allele and a normal pattern on Southern blot analysis were found in combination with the FRAXAC2 and DXS297 allele of the maternal at risk haplotype. A second chorionic villus sampling was performed giving identical results on DNA analysis and, in addition, expression of FMRP was shown by immunohistochemistry. We concluded that the male fetus was not affected with the fragile X syndrome. Subsequent detailed haplotype analysis showed a complex recombination pattern resembling either gene conversion or a double crossover within a 20 kb genomic region.