Fragile X Syndrome Premutation Screening
Clinical Background
Fragile X syndrome is the most common inherited disease of mental retardation. The syndrome occurs in approximately 1 in 3,600 males and 1 in 4,000–6,000 females. Around 1 in 250 females carry the premutation.
Women with a family history of fragile X-related disorders, unexplained mental retardation or developmental delay, autism, or premature ovarian insufficiency are candidates for genetic counseling and fragile X premutation carrier screening.
Pathogenesis
Fragile X syndrome is transmitted as an X-linked disorder that caused by expansion of a repeated trinucleotide segment of DNA, CGG of the fragile X mental retardation 1 (FMR1) gene.
The number of CGG repeats varies among individuals and has been classified into four groups depending on the repeat size.
Number of (CGG) Repeats |
Genotype |
Phenotype |
< 45 |
Normal |
Unaffected |
45-54 |
Intermediate |
Unaffected |
55-200 |
Premutation |
Unaffected Carrier for Fragile X syndrome |
>200 |
Full mutation |
Fragile X syndrome |
A person with 55–200 repeats usually is phenotypically normal and is said to have a premutation. When more than 200 repeats are present, an individual has a full mutation that results in the full expression of fragile X syndrome in males and variable expression in females secondary to X chromosome inactivation.
Important for gene screening
Genetic analysis is the preferred method of diagnosis for fragile X syndrome. Prenatal testing for fragile X syndrome should be offered to known carriers of the fragile X premutation or full mutation.