HomeGeneticsGeneDUX4 gene
Back to Gene
DUX4 gene
Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Gene

DUX4 gene

The DUX4 gene is normally silenced in adult tissues, but its abnormal activation due to genetic changes in the D4Z4 region is the primary cause of facioscapulohumeral muscular dystrophy.

Normal Function

The DUX4 gene is located in a region of chromosome 4 known as D4Z4. This region consists of repeated segments that are normally hypermethylated, a process that silences the genes within them. In most adult cells, the DUX4 gene is turned off. It is only active during early development and in the testes of adult males. A functional pLAM sequence is required for the production of the DUX4 protein; chromosomes with this sequence are called "permissive," while those without it are "non-permissive."

Health Conditions Related to Genetic Changes

Facioscapulohumeral muscular dystrophy

Facioscapulohumeral muscular dystrophy (FSHD) is caused by the hypomethylation of the D4Z4 region, which prevents the DUX4 gene from being properly silenced. This leads to the production of the DUX4 protein in tissues where it should be absent, such as adult muscle cells.

  • FSHD1: Caused by an abnormally shortened (contracted) D4Z4 region (1 to 10 repeats).
  • FSHD2: Most often caused by mutations in the SMCHD1 gene, which is responsible for the normal hypermethylation of the D4Z4 region.

Disease occurs only when this hypomethylation happens on a "permissive" chromosome 4, allowing the DUX4 protein to be produced. The protein is believed to interfere with the activity of other genes, ultimately leading to progressive muscle weakness and atrophy.

Other Names for This Gene

  • double homeobox 4-like
  • double homeobox protein 10
  • double homeobox protein 4
  • double homeobox protein 4/10

Frequently Asked Questions

FSHD1 is caused by a shortened D4Z4 repeat array (1–10 repeats) on a permissive chromosome 4, leading to inappropriate DUX4 expression. FSHD2 results from mutations in SMCHD1 that reduce methylation of the D4Z4 region; the disease only manifests when the hypomethylated region is on a permissive chromosome, again allowing DUX4 to be expressed in muscle cells. Both conditions ultimately produce the same muscle‑weakening phenotype, but the underlying genetic trigger differs.
Diagnosis starts with clinical evaluation of characteristic muscle weakness. Genetic testing then measures the number of D4Z4 repeats on chromosome 4 and checks for the presence of the pLAM sequence (permissive allele). Southern blotting, PCR‑based sizing, or next‑generation sequencing panels are commonly used. A repeat count of 1–10 with a permissive allele confirms FSHD1; SMCHD1 mutation testing plus repeat sizing confirms FSHD2.
Physical therapy focused on stretching and strengthening, especially of scapular stabilizers, can improve function. Occupational therapy can aid in daily activities. Emerging treatments include antisense oligonucleotides targeting DUX4 mRNA, gene‑editing approaches, and small molecules that restore methylation. Until these are widely available, symptom‑based management and regular monitoring are key.
Carriers of a shortened D4Z4 repeat on a permissive chromosome have a high risk of developing FSHD, but penetrance is variable. Some carriers may remain asymptomatic or have very mild symptoms, while others experience progressive muscle weakness. Genetic counseling and periodic clinical assessment are recommended for at‑risk relatives.
Source: MedlinePlus, National Library of Medicine

MedlinePlus brings together authoritative health information from the National Library of Medicine (NLM), the National Institutes of Health (NIH), and other government agencies and health-related organizations.

kontakt@hittavard.se

Ⓒ 2024. Alla rättigheter förbehålls av juxt ab

Sök
Om ossVillkor och policyVanliga frågorKontakta oss