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Long-read Genome Sequencing for the Molecular Diagnosis of Dystonia

Key facts

Who runs it
University Hospital, Strasbourg, France
Where
France4 sites in 1 countryChoose a country to see its sites
Trial code
Status
Recruiting
People taking part
150 people, planned
Started
22 Apr 2026
Expected to end
Aug 2030
Type of study
Interventional
Treatments tested
  • Long-read whole genome sequencing
Record updated
20 May 2026

Who can take part

Sex
Women and men
Healthy volunteers
Cannot take part

The registry criteria, word for word

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Who can take part

  • Index case affected by familial dystonia (≥1 first-degree relative affected) and/or sporadic early-onset dystonia (symptom onset before age 50), meeting the criteria of the PFMG-2025 program
  • Index case who has undergone short-read genome sequencing, which did not lead to a molecular diagnosis
  • Ability to understand and sign informed consent by the index case and/or their parents or legal guardians for patients under 18 years of age
  • Availability of a blood sample from the index case and at least two relatives, either affected or unaffected
  • Symptomatic or asymptomatic relative of an index case, who has also undergone short-read genome sequencing without a conclusive molecular diagnosis
  • Ability to understand and sign informed consent

Who cannot take part

  • Index case and their parents presenting with a condition that, in the opinion of the investigator, would contraindicate participation in the study
  • Suspected non-genetic etiology (e.g., perinatal hypoxic-ischemic injury, kernicterus, history of severe head trauma or central nervous system infection)
  • Index case or relatives who are not affiliated with or not beneficiaries of a social security scheme

This trial has no sites in United States.

It has sites in one country. Choose a country to see its sites.

About the trial

What the trial wants to find out

Dystonia is a motor disorder caused by involuntary, intermittent, or sustained muscle contractions, leading to abnormal movements or postures. It can affect any body region and often results in significant functional disability and healthcare burden. Although its familial nature was recognized early on, the advent of high-throughput DNA sequencing has dramatically increased the identification of dystonia-associated genes. Dystonia now encompasses all modes of inheritance-autosomal dominant (e.g., TOR1A, KMT2B), autosomal recessive, X-linked, and mitochondrial-and over 100 genes have been implicated. Many forms involve structural variants (SVs) or copy number variations (CNVs), which are challenging to detect using standard short-read sequencing (srWGS).

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Molecular diagnosis is essential, ending the diagnostic odyssey and enabling genetic counseling, prognosis, reproductive planning, and-in some cases-targeted therapies. For instance, GNAO1-related dystonia may respond to deep brain stimulation, while dopa-responsive dystonia benefits from levodopa.

Despite advances, srWGS has key limitations, especially for detecting repeat expansions, SVs, and phasing alleles. This likely explains the low diagnostic yield in dystonia compared to other neurological disorders, with over 70% of cases remaining unsolved.

Long-read sequencing (lrWGS), such as Oxford Nanopore technology, overcomes many of these challenges by reading native DNA fragments thousands of bases long. It enables comprehensive detection of SNVs, indels, SVs, CNVs, methylation changes, and repeat expansions-including known and newly discovered pathogenic expansions (e.g., in NOTCH2NLC). It also allows phasing without parental samples, which is crucial in recessive cases.

The investigators propose that lrWGS could significantly increase the diagnostic yield in dystonia, improving patient care, enabling appropriate genetic counseling, and paving the way for personalized treatment strategies.

The group in the trial

  • Dystonia patients without molecular diagnosisTreatment being tested

    Long-read genome sequencing for identification of genetic causes in dystonia patients without molecular diagnosis

    Treatment: Long-read whole genome sequencing

Questions to ask the study team

  1. How often do I need to come in, and for how long each time?
  2. Are travel costs paid?
  3. Can I keep my own doctor?
  4. What happens if I want to stop?

Contact the study team: see the registry record → Contacts and Locations

Print a page for my doctor

Data and sources

Registry record
Listed on ClinicalTrials.gov.
Official title
Evaluation of the Value of Long-read Genome Sequencing for the Molecular Diagnosis of Dystonia: a Prospective Multicenter Study
Record updated
20 May 2026