Fragile X syndrome Fragile X syndrome Originally described by Martin and Bell in 1943, and sometimes referred to as Martin-Bell Syndrome. It is the most common X-linked form of mental retardation, and the second most common form of mental retardation after Down's syndrome.
Expression is variable, with mental retardation the most common feature.
Both males and females can be affected, but females are usually not as severe in phenotype. Most people with fragile X syndrome have a long trinucleotide repeat in the FMR1 gene that inhibits transcription. However, there are other mutations of FMR1 that give the same phenotype, but without evidence of a fragile site or broken chromosomes. So, the chromosome breakage is probably a secondary effect of the mutation rather than a primary cause of the mutant phenotype, and the primary cause of the mutant phenotype is altered or missing FMR1 protein. This TNR is in the 5' untranslated region of the FMR1 gene.