As shown in the video and image above:
- When a mother passes on a premutation, it’s often a larger version of the mutation, i.e., a full mutation.
- If a mother passes on a full mutation, it will remain a full mutation.
- When a father passes a premutation on to his daughters, it remains a premutation, and does not expand to a full mutation.
- In most women with a mutation, it only appears in one of her X chromosomes, which means her second X chromosome is normal. Thus she has a 50% chance of passing on either her normal X chromosome or her mutation (premutation of full mutation) in each pregnancy.
- Because fathers who carry the premutation have only one X chromosome, they will pass it on to all of their daughters
- Because fathers only pass their Y chromosome to their sons, fathers with the premutation will not pass it on to their sons.
The Fragile X Premutation
55–200 CGG Repeats
Approximately 1 in 151 females and 1 in 468 males carry the FMR1 premutation. They are known as “premutation carriers,” often shortened to “premutations.” Premutations are defined as having 55–200 CGG repeats and can occur in both males and females. (Also see: What Defines a Carrier.)
A common feature of premutations is that the gene can change sizes over generations, potentially expanding to a full mutation in subsequent generations.
The chance of the premutation expanding to a full mutation is related to the size of the mother’s premutation — the larger the mother’s CGG repeat number, the higher the chance that it will expand to a full mutation if passed on.
Typically, the premutation has no immediate and observable impact on a person’s appearance or health. However, some females with a premutation will experience Fragile X-associated primary ovarian insufficiency (FXPOI), which causes infertility, irregular or missed menstrual cycles, and/or early menopause.
Additionally, some older adults with a premutation may develop a neurological condition called Fragile X-associated tremor/ataxia syndrome (FXTAS), an adult onset neurodegenerative disorder. This is most common in males over 50.
FXTAS and FXPOI are part of the family of conditions called Fragile X-associated disorders. Fragile X-associated disorders are a group of conditions called trinucleotide repeat disorders.
The Fragile X Full Mutation
> 200 CGG Repeats
Most full mutation CGG expansions have some degree of methylation (the process that “turns off” the gene). Males with a full mutation will have Fragile X syndrome, though with varying degrees of severity.
About 65%-70% of females with a full mutation will exhibit some difficulties with cognitive, learning, behavioral, or social functioning, and may also have some of the physical features of Fragile X syndrome (such as large ears or a long face).
The remaining 30%-35% are at risk to develop mental health issues such as anxiety or depression, or they may have no observable effects of the full mutation.
Also see: The Unique Challenges for Females with Fragile X Syndrome.