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.

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 < 45, grey zone 45–54, premutation 55–200 (risk of ovarian insufficiency and FXTAS tremor-ataxia), full mutation > 200.
Diagnosis uses PCR to count repeats and Southern blot (or specialised PCR) for large expansions and methylation status.

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.

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.

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

Sources: Fragile X syndrome: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); Huntington's disease: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); FXN gene: MedlinePlus Genetics (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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Representative model, for educational purposes only.