Fragile X syndrome is caused by a mutation on the FMR1 gene on the X chromosome. It is the most common inherited cause of intellectual disability. The mutation involves a trinucleotide CGG repeat that silences the FMR1 gene, preventing production of the FMRP protein needed for normal brain development. Affected individuals have intellectual disabilities, autism-like behaviors, anxiety, and other issues. Males typically have more severe symptoms than females. While there is no cure, early intervention and therapies can help manage symptoms.

1. Fragile X Syndrome
(FXS)

2. Course Code: GEB204
Semester: Fall 2018
Group Members :
MD. Samourah Hossain Khan
ID: 2014-2-77-003
Asma Hossain
ID: 2015-2-77-004
Syeda Nousin Bedora
ID: 2015-2-77-016
Farjana Akber
ID: 2015-2-77-021

3. Introduction
• Most common inherited
intellectual disability.
• A X-linked disease.
• A trinucleotide (CGG) repeat
disorder.
• Can affect both genders.
• Most frequent cause of inherited
mental retardation after down
syndrome.
• Also known as the most
common single gene cause of
autism.

4. How Common Is
FRAGILE X SYNDROME?
• 1 in 3600 to 4000 males in the world are born with
the full mutation.
• 1 in 4000 to 6000 females in the world are born
with the full mutation.
• 1 in 800 men in the world are carriers of the
Fragile X premutation.
• 1 in 260 women in the world are carriers of the
Fragile X premutation.

5. Why It Is Called
‘FRAGILE X SYNDROME’
• A rare, folic acid
sensitive site at
Xq27.3
• Tends to break under
stress
• Unstable CGG
repeats at the
‘FRAGILE SITE’

6. Epigenetic Causes
• FMR1 gene on the X chromosome makes a protein called
fragile x mental retardation protein (FMRP) .
• FMRP – protein required for normal neural development.
Absence of FMRP leads to abnormalities in brain
development and function.
• In almost every affected individual, this mutation is a repeating
CGG nucleotide sequence in the gene. This disables the
FMR-1 gene, causing an absence of the FMRP protein and
leading to mental retardation and other effects of FX
Syndrome.
FX Syndrome is caused by a
mutation of the Fragile X Mental
Retardation 1 (FMR1) gene
located on the end of the X
chromosome.

7. Epigenetic Causes
• FXS depends on repeatation of CGG trinucleotide in FMR1
gene where:
At this threshold of about 200 repeats, referred to as the “full
mutation,” a remarkable phenomenon occurs where
the FMR1 gene itself becomes heavily CpG methylated and
shifts chromatin marks from a euchromatic state to a fully
heterochromatic state. The result is the transcriptional silencing
of FMR1 and the absence of the encoded protein, FMRP, leading
to the clinical picture of fragile X syndrome.

9. Molecular Basis of FXS
FMRP is a RNA
binding protein.
•It affects-
1. mGluR signaling
2. Dopamine
pathways
3. GABA pathways

10. Inheritance Pattern
Inherited in an X-linked dominant pattern.
• Mother → premutation or full mutation → passes
to both daughter and son.
• Mother → 50% chance of passing mutant X.
• Father → premutation → passes only to
daughters.

13. Symptoms
• Intellectual disabilities..
• Anxiety and unstable mood.
• Autistic behaviors, such as hand-flapping and not making eye contact.
• Sensory integration problems, such as hypersensitivity to loud noises or
bright lights.
• Speech delay.
• Seizures (epilepsy) affect about 25% of people with Fragile X syndrome.
 Physical Signs
• Long face, large prominent ears, flat feet.
• Hyper extensible joints, especially fingers.
• Low muscle tone.
• Males may have large testes after puberty.
 Females usually have milder symptoms than males.

15. FXS Treatments
• MPEP negative mediator which blocks mGluR.
• Lithium blocks inositol phosphate (IP) turnover , also inhibits
GSK3B activity.
• CX516 Ampakine increases AMPA activity and redistributes
AMPA receptors to the synaptic membrane through the activation
of BDNF.

16. Treatments and Prevention
There is no specific treatment for FXS.
• Therapy treatments
 Speech-language therapy
 Physical therapy
 Behavioral therapy
• Drugs- mGluR5 antagonist, Mavoglurant and
Diproglurant, Fenobam etc.
• Genetic counseling before family planning.

17. Conclusion
• Caused by FMR1 gene mutation which is a result of 200+ triple
CGG nucleotide sequence repeats. FXS mostly inherited cause of
mental retardation.
• There is no possible replacement way of FMR1 protein with
artificial protein.
• Early intervention, special education and vocational training can
help to improve their condition. Special education and anticipatory
management can also decrease their behavior problems.

18. Thank You!!!
Any Questions???