BRC researchers have identified the genetic cause of primary isolated dystonia, a type of inherited dystonia.
Dystonia itself is a common neurological disorder characterised by involuntary muscle spasms which affects approximately 70,000 people in UK. Currently, there are no cures for this disabling condition.
Some forms of primary isolated dystonia are inherited in an autosomal-recessive manner, meaning two copies of an abnormal gene must be present in order for the disease to develop. Until now, no genetic cause of autosomal recessive primary isolated dystonia has ever been identified.
The researchers identified recessive mutations in the gene HPCA as the cause of childhood onset isolated dystonia in three blood related siblings from a family of Middle Eastern origin. Mutations in the same gene were also detected in a second family exhibiting young-onset dystonia, confirming HPCA as the responsible gene.
The team, led by Professor Nicholas Wood, used a gene mapping method called homozygosity mapping and a testing method called whole-exome sequencing at the UCL Institute of Neurology to look closely at the patients’ entire genetic code by taking blood samples. This allowed them to detect rare genetic variants and identify an underlying genomic cause of primary isolated dystonia.
Individuals who are ‘homozygous’ for a certain gene carry two copies of the same allele.
Professor Wood said: “Homozygosity mapping is a well-established method, whereby we can identify the region of the genome which contains the causative gene. From there we combine this with large scale sequencing information to help identify the specific mutation which causes this poorly understood condition.”
The team anticipate that by finding this HPCA gene as responsible for primary isolated dystonia new therapeutic pathways may be possible. Professor Wood said: “It is important to discover where the gene is expressed which may help deepen our understanding of the causes of dystonia”.
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