AUTHOR=Jin Chunlei , Zhang Xiangdong , Lei Qiang , Chen Penglong , Hu Hui , Shen Shuangshuang , Liu Jiao , Ye Shixuanbao 

TITLE=Case report: genetic analysis of a novel frameshift mutation in FMR1 gene in a Chinese family

JOURNAL=Frontiers in Genetics

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2023.1228682

DOI=10.3389/fgene.2023.1228682

ISSN=1664-8021

ABSTRACT=<p>Fragile X syndrome (FXS) [OMIM 300624] is a common X-linked inherited syndrome with an incidence only second to that of trisomy 21. More than 95% of fragile X syndrome is caused by reduced or absent fragile X intellectual disability protein 1 (FMRP) synthesis due to dynamic mutation expansion of the CGG triplet repeat in the 5′UTR and abnormal methylation of the <italic>FMR1</italic> (fragile X messenger ribonucleoprotein 1) gene [OMIM 309550]. Less than 5% of cases are caused by abnormal function of the FMRP due to point mutations or deletions in the <italic>FMR1</italic> gene. In a proband with clinical suspicion of FXS and no CGG duplication, we found the presence of c.585_586del (p.Lys195AsnfsTer8) in exon 7 of the <italic>FMR1</italic> gene using whole exome sequencing (WES). This variant resulted in frameshift and a premature stop codon after 8 aberrant amino acids. This variant is a novel pathogenic mutation, as determined by pedigree analysis, which has not been reported in any database or literature.</p>