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Novel point mutation within intron 10 of FMR‐1 gene causing fragile X syndrome
Author(s) -
Wang YiChun,
Lin MeiLing,
Lin Shio Jean,
Li YuehChun,
Li ShuanYow
Publication year - 1997
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/(sici)1098-1004(1997)10:5<393::aid-humu10>3.0.co;2-v
Subject(s) - exon , biology , genetics , point mutation , intron , mutation , gene , fragile x syndrome , microbiology and biotechnology , untranslated region , rna
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 14 th 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. Hum Mutat 10:393–399, 1997. © 1997 Wiley‐Liss, Inc.