Fragile X syndrome

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Fragile X syndrome


Genetic disorders


Alagille syndrome (NORD)

Familial adenomatous polyposis

Familial hypercholesterolemia

Hereditary spherocytosis

Huntington disease

Li-Fraumeni syndrome

Marfan syndrome

Multiple endocrine neoplasia

Myotonic dystrophy


Polycystic kidney disease

Treacher Collins syndrome

Tuberous sclerosis

von Hippel-Lindau disease




Cystic fibrosis

Friedreich ataxia

Gaucher disease (NORD)

Glycogen storage disease type I

Glycogen storage disease type II (NORD)

Glycogen storage disease type III

Glycogen storage disease type IV

Glycogen storage disease type V


Krabbe disease


Mucopolysaccharide storage disease type 1 (Hurler syndrome) (NORD)

Niemann-Pick disease type C

Niemann-Pick disease types A and B (NORD)

Phenylketonuria (NORD)

Polycystic kidney disease

Primary ciliary dyskinesia

Sickle cell disease (NORD)

Tay-Sachs disease (NORD)

Wilson disease

Cri du chat syndrome

Williams syndrome

Angelman syndrome

Prader-Willi syndrome

Beckwith-Wiedemann syndrome

Mitochondrial myopathy

Klinefelter syndrome

Turner syndrome

Fragile X syndrome

Friedreich ataxia

Huntington disease

Myotonic dystrophy

Down syndrome (Trisomy 21)

Edwards syndrome (Trisomy 18)

Patau syndrome (Trisomy 13)

Alport syndrome

Fragile X syndrome

Fabry disease (NORD)

Glucose-6-phosphate dehydrogenase (G6PD) deficiency


Lesch-Nyhan syndrome

Mucopolysaccharide storage disease type 2 (Hunter syndrome) (NORD)

Muscular dystrophy

Ornithine transcarbamylase deficiency

Wiskott-Aldrich syndrome

X-linked agammaglobulinemia

Autosomal trisomies: Pathology review

Miscellaneous genetic disorders: Pathology review

Muscular dystrophies and mitochondrial myopathies: Pathology review


Fragile X syndrome


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USMLE® Step 1 questions

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High Yield Notes

5 pages


Fragile X syndrome

of complete


USMLE® Step 1 style questions USMLE

of complete

A 6-year-old adopted boy is brought to the physician to discuss his genetic testing results. The child had been having difficulties communicating with others in the classroom and was subsequently diagnosed with autism spectrum disorder and an intellectual disability. The genetic testing confirms a diagnosis of Fragile X syndrome. Which of the following family pedigrees represents this patient’s biological family history? (Arrows indicating the patient).  

External References

First Aid








Autism spectrum disorder p. 580

fragile X syndrome p. 60

Fragile X syndrome p. 60

chromosome association p. 62

dominant, inheritance of p. 57

Mitral valve prolapse p. 298

fragile X syndrome p. 60


With Fragile X syndrome, sometimes just called Fragile X, the “X” refers to the X chromosome, where the disease gene is located.

The “fragile” refers to the fact that under a microscope, the X chromosome looks fragile or broken at the site of the mutation.

That’s because the chromatin which makes up the chromosome gets really condensed at that point.

Fragile X is a genetic disease that affects various organ systems.

Now, the gene for Fragile X is called FMR1, which stands for Fragile X mental retardation 1.

Mental retardation is the old term for intellectual disability, which is one of the key features of Fragile X syndrome.

The FMR1 gene has a triplet repeat, or trinucleotide repeat, which means that a group of three DNA nucleotides is repeated multiple times in a row.

In FMR1, it’s the nucleotides cytosine, guanine, and guanine, or CGG.

These CGGs are found in the 5’ untranslated region of FMR1.

A 5’ untranslated region is the part of DNA at the beginning of the gene that’s made into mRNA but not protein, and helps modulate gene expression.

Just upstream from the 5’ untranslated region is FMR1‘s promoter, the region that causes the gene to be transcribed to mRNA, which is usually turned on.

Expressed FMR1 mRNA gets translated into Fragile X mental retardation protein, or FMRP, and it helps in development of the brain and other tissues.

In Fragile X syndrome, there is a repeat expansion, meaning there’s an increased number of CGG repeats in the gene.

This repeat expansion is caused by slipped mispairing, which is where the enzyme DNA polymerase gets confused when copying a repetitive sequence.

DNA polymerase loses its place among the FMR1 triplet repeats and goes back to recopy what it already just copied.

This is like getting lost in a video and watch the same part over and over.

But since DNA polymerase is making copies, the effect is an increase, or expansion, of the number of repeats.

The normal number of CGG triplets is 5-44.

Alleles with 45 to 54 CGG repeats are called intermediate expansion alleles and they don’t cause any symptoms.

Alleles with 55 to 200 CGGs are called premutation alleles, and they can cause some mild symptoms.

Finally if an allele has over 200 CGGs, then it’s considered a full fragile X syndrome mutation and can make the chromosome take on its distinctive look.


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