Screening with the FMR1 protein test among mentally retarded males.
The fragile X syndrome is characterized by X-linked mental retardation with additional features such as a long face with large protruding ears, macroorchidism, and eye-gaze avoidance. The disorder is caused by an abnormally expanded CGG repeat within the first exon of the fragile X mental retardation (FMR1) gene that is associated with shutdown of transcription and absence of the fragile X mental retardation protein (FMRP). Detection of patients and carriers of the fragile X syndrome is done by DNA analysis of the CGG repeat, whereas the FMRP antibody test allows rapid detection of male patients using bloodsmears. In a screening program for the fragile X syndrome in the southwest of the Netherlands, 412 males with mental retardation of unknown cause were subjected to the protein test. The patients were scored for fragile X features and their DNA tested for the FMR1 mutation, as reported previously. The FMRP test detected two fragile X patients with a repeat expansion in FMR1, whereas normal protein expression was observed in all the retarded male patients with a normal repeat. The FMRP test was found to be suitable for screening among a large population of retarded males. The results also suggest that mutations other than the CGG repeat leading to absence of detectable FMRP are apparently rare among mentally retarded males.
de Vries
B B
BB
Department of Clinical Genetics, University Hospital Dijkzigt and Erasmus University, Rotterdam, The Netherlands. devries@kgen.fgg.eur.nl
Mohkamsing
S
S
van den Ouweland
A M
AM
Halley
D J
DJ
Niermeijer
M F
MF
Oostra
B A
BA
Willemsen
R
R
D000906:Antibodies; D051860:Fragile X Messenger Ribonucleoprotein 1; D005600:Fragile X Syndrome / Q000175:diagnosis*; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D008607:Intellectual Disability / Q000209:etiology*; D008297:Male; D009419:Nerve Tissue Proteins / Q000032:analysis*; D016601:RNA-Binding Proteins
D000906:Antibodies; D051860:Fragile X Messenger Ribonucleoprotein 1; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; C497683:FMR1 protein, human