In 1991, the fragile X mental retardation 1 (FMR1) gene was discovered (fig. Despite these differences, this high rate of autism diagnosis makes the fragile X mutation the leading known single-gene mutation causing autism (reviewed in Hagerman ). However, it has recently been reported that there are significant differences in the profile of social and communicative symptomatology in FXS compared with individuals diagnosed with idiopathic autism. Interestingly, while some FXS patients tend to be very social and interested in other people, approximately 30% of those with FXS are diagnosed with autism, and pervasive developmental disorders not otherwise specified occur in an additional 30% (reviewed in Hagerman ).

Seizures (epilepsy) also occur in about 25% of people with FXS. In addition, macroorchidism, long face and high arched palate are present in adulthood. Most FXS patients also present some physical features including prominent ears, soft skin, flat feet, and loose connective tissue that leads to hyperextensible joints, especially fingers. Also, both males and females usually present behavioral and emotional problems, even with a normal IQ, such as attention deficit hyperactivity disorder, anxiety, unstable mood, impulsivity, aggressiveness, poor eye contact, shyness, self-talk, hyperarousal to sensory stimuli, hand flapping, and hand biting (reviewed in Hagerman ). Females are usually less affected as they have two X chromosomes therefore, random X inactivation in each cell determines the intellectual level and physical involvement caused by the fragile X mutation. While most boys have intellectual disabilities, only one third to one half of girls have significant intellectual impairment the rest have either a normal IQ or lesser learning disabilities (reviewed in Hagerman ). Males are typically more severely affected than females.

FXS is a neurodevelopmental disorder accounting for the most common cause of inherited mental impairment ranging from intellectual disability to learning problems. Further cytological studies of males from the original Martin and Bell pedigree showed that they possessed the fragile X site, and intellectual disability associated with a fragile X chromosome was then termed Martin-Bell syndrome, today known as FXS.įXS is an X-linked inheritable disease, and it is one of a group of genetic conditions that also includes fragile X-associated tremor/ataxia syndrome and fragile X-associated primary ovarian insufficiency, collectively called fragile X. Sutherland discovered that using the medium 199 gained instant access to the fragile sites, which helped develop the first test for FXS. In 1977, Grant Sutherland, who was studying the occurrence of fragile sites, discovered that the ability to detect fragile sites was dependent on the chemicals used to study patients’ chromosomes. This constriction made the X chromosome appear broken, and therefore became known as the ‘fragile’ X chromosome. Lubs observed and described a constriction near the end of the long arm of the X chromosome (Xq27.3) in cultured cells from 4 intellectually disabled males and 2 mentally normal females. This study led the geneticist Herbert Lubs in 1969 to microscopically examine the X chromosome from family members with intellectual disability. The first steps toward discovery of the human genetic disease fragile X syndrome (FXS) began in 1943 in a pedigree reported by James Purdon Martin, an English physician, and Julia Bell, an English geneticist, who together observed intellectual disability in 11 males consistent with an X-linked problem.

Normal fear vs pathological fear