Array-based FMR1 sequencing and deletion analysis in patients with a fragile X syndrome-like phenotype.
BACKGROUND
Fragile X syndrome (FXS) is caused by loss of function mutations in the FMR1 gene. Trinucleotide CGG-repeat expansions, resulting in FMR1 gene silencing, are the most common mutations observed at this locus. Even though the repeat expansion mutation is a functional null mutation, few conventional mutations have been identified at this locus, largely due to the clinical laboratory focus on the repeat tract.


RESULTS
To more thoroughly evaluate the frequency of conventional mutations in FXS-like patients, we used an array-based method to sequence FMR1 in 51 unrelated males exhibiting several features characteristic of FXS but with normal CGG-repeat tracts of FMR1. One patient was identified with a deletion in FMR1, but none of the patients were found to have other conventional mutations.


CONCLUSIONS
These data suggest that missense mutations in FMR1 are not a common cause of the FXS phenotype in patients who have normal-length CGG-repeat tracts. However, screening for small deletions of FMR1 may be of clinically utility.
Collins
Stephen C
SC
Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia, United States of America.
Coffee
Brad
B
Benke
Paul J
PJ
Berry-Kravis
Elizabeth
E
Gilbert
Fred
F
Oostra
Ben
B
Halley
Dicky
D
Zwick
Michael E
ME
Cutler
David J
DJ
Warren
Stephen T
ST
D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics*; D005600:Fragile X Syndrome / Q000235:genetics*; D017353:Gene Deletion; D006801:Humans; D008297:Male; D009154:Mutation; D020125:Mutation, Missense; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA; D019680:Trinucleotide Repeat Expansion
D051860:Fragile X Messenger Ribonucleoprotein 1; C497683:FMR1 protein, human