The Future of Fragile X Syndrome: CDC Stakeholder Meeting Summary.

* Abbreviations: ASD — : autism spectrum disorder CDC — : Centers for Disease Control and Prevention FMR1 — : fragile x mental retardation FMRP — : fragile X mental retardation FXD — : fragile X–associated disorder FXS — : fragile X ID — : intellectual disabilityFragile X syndrome (FXS) is the most common known inherited cause of intellectual disability (ID). Males and females with FXS exhibit a wide range of intellectual ability and may experience various degrees of emotional, behavioral, sensory, learning, and social difficulties. In 1991, the gene responsible for FXS was identified on the X chromosome at q27.3 and named fragile x mental retardation 1 ( FMR1 ) gene.1 FXS and fragile X–associated disorders (FXD) are caused by a trinucleotide repeat (CGG) expansion mutation in the promoter region (exon 1) of FMR1 . Affected individuals with the full FXS mutation have u003e200 repeats. When the full mutation is present, FMR1 methylation occurs during gestation, which causes silencing of gene transcription.2 This in turn leads to a reduction or absence of fragile X mental retardation protein (FMRP), which is needed for brain development and function. Most males with FXS have ID. A small number of males have less impaired function due to methylation patterns or mosaicism. In females, FMRP levels depend on the X activation ratio, or the percent of cells expressing the normal allele on the active X chromosome,3 resulting in a range of normal intellectual ability to moderate ID.Over the past 2 decades, scientists have made significant advancements in identifying and describing genetic, molecular, and cellular underpinnings of FXS, allowing for a more precise diagnosis of this condition. The present challenge is to move from accurate diagnosis to public health action for FXS, requiring better understanding of the natural history of FXS, … Address correspondence to Julie Bolen, PhD, MPH, National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, 4770 Buford Hwy (E-88), Atlanta, GA 30341. E-mail: jcr2{at}cdc.gov