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[Biochemistry](https://durgical.com/en/biochemistry/) · Topic

# Trinucleotide repeat expansion disorders

Some diseases come from a three-base unit repeated too many times; the repeat tends to grow from one generation to the next.

Updated 2026-11-01

## Key facts

- Huntington: CAG in HTT (exon, polyglutamine), autosomal dominant, expands mainly through the father.
- Fragile X: CGG in the 5' untranslated region of FMR1, X-linked, expands through the mother; > 200 repeats silence the gene.
- Friedreich ataxia: GAA in the FXN intron (frataxin), autosomal recessive; it lowers transcription.
- Myotonic dystrophy type 1: CTG in the 3' untranslated region of DMPK; the toxic RNA traps splicing factors.
- Anticipation: more repeats → earlier and more severe onset.

## In detail

- Expansion mechanism: repeats form hairpins on the lagging strand during replication or repair, and the polymerase 'slips'.
- Repeats in exons coding for glutamine (CAG): the protein with a long polyglutamine tract aggregates and is toxic (gain of function). Includes Huntington and several spinocerebellar ataxias.
- Repeats outside exons: loss of function by silencing (fragile X, Friedreich) or toxic RNA (myotonic dystrophy).
- Fragile X ranges: normal 200.
- Diagnosis uses PCR to count repeats and Southern blot (or specialised PCR) for large expansions and methylation status.

## Clinical notes

- Genetic counselling is key: a silent premutation in the mother can become a full mutation in her child.
- Age at onset of Huntington disease is inversely related to the number of CAG repeats.

## Related conditions

- [Fragile X syndrome](https://durgical.com/en/conditions/fragile-x-syndrome/)
- [Huntington disease](https://durgical.com/en/conditions/huntington-disease/)

## Related

- [Types of mutations](https://durgical.com/en/biochemistry/topics/types-of-mutations/)
- [Epigenetics: DNA and histone methylation](https://durgical.com/en/biochemistry/topics/epigenetics-dna-and-histone-methylation/)
- [DNA replication: the replication fork](https://durgical.com/en/biochemistry/topics/dna-replication-the-replication-fork/)

## Test yourself

Think of the answer, then tap the question to see it.

## Which triplet expands in Huntington disease, and which protein does it change?

CAG in the HTT gene; it gives a huntingtin with an overly long polyglutamine tail.

## Why does the fragile X CGG expansion cause loss of function?

More than 200 repeats lead to methylation of the FMR1 promoter, which stops being transcribed.

## Which techniques measure a repeat expansion?

PCR to count repeats, and Southern blot or specialised PCR for large expansions and methylation.

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Educational information, not medical advice. For any symptom, see a health professional.

Sources: [Fragile X syndrome: MedlinePlus Genetics](https://medlineplus.gov/genetics/condition/fragile-x-syndrome/) (MedlinePlus, US National Library of Medicine, 2026); [Huntington's disease: MedlinePlus Genetics](https://medlineplus.gov/genetics/condition/huntingtons-disease/) (MedlinePlus, US National Library of Medicine, 2026); [FXN gene: MedlinePlus Genetics](https://medlineplus.gov/genetics/gene/fxn/) (MedlinePlus, US National Library of Medicine, 2026); Textbook of Biochemistry for Medical Students, 6th ed. (Jaypee Brothers Medical Publishers (Vasudevan DM, Sreekumari S, Vaidyanathan K), 2011).

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License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/biochemistry/topics/trinucleotide-repeat-expansion-disorders/