title: Novel point mutation within intron 10 of FMR-1 gene causing fragile X syndrome.
abstract: The majority of cases involving fragile X syndrome are due to expansion of a (CGG)n trinucleotide repeat at the 5' untranslated region of the FMR-1 gene. Deletion and intragenic loss of function mutations of the FMR-1 gene also have been reported. Here, we report a C to T point mutation at the 14th nucleotide in intron 10 of the FMR-1 gene in three unrelated fragile X patients. However, the (CGG)n repeat of FMR-1 in those patients does not expand. To determine the effect of this mutation on the patients' FMR-1 transcripts, total RNA from peripheral blood cells was reverse transcribed and amplified by polymerase chain reaction (RT-PCR). Direct and subcloned sequencing of the RT-PCR products revealed that the transcripts from the allele with C to T mutation skip exon 10 entirely, resulting in a joining of exons 9 and 11. Deletion of exon 10 results in frame-shift and premature termination of translation, which removes the highly conserved region that encoding the KH2 and RGG box domains of FMRP. Interestingly, a male of the three patients has another G to A substitution in exon 15. However, the intron 10 mutation is sufficient for development of fragile X syndrome.
authors.affiliation: Molecular Genetics and Cytogenetics Laboratory, Chung Shan Medical and Dental College, Taichung, Taiwan.
authors.forename: Y C
authors.initials: YC
authors.lastname: Wang
authors.forename: M L
authors.initials: ML
authors.lastname: Lin
authors.forename: S J
authors.initials: SJ
authors.lastname: Lin
authors.forename: Y C
authors.initials: YC
authors.lastname: Li
authors.forename: S Y
authors.initials: SY
authors.lastname: Li
mesh_terms: D000293:Adolescent; D017398:Alternative Splicing; D001483:Base Sequence; D002648:Child; D018076:DNA, Complementary; D051860:Fragile X Messenger Ribonucleoprotein 1; D005600:Fragile X Syndrome / Q000235:genetics*; D006801:Humans; D007438:Introns; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics*; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D016601:RNA-Binding Proteins; D018911:Trinucleotide Repeats
chemical_list: D018076:DNA, Complementary; D051860:Fragile X Messenger Ribonucleoprotein 1; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; C497683:FMR1 protein, human