Genetic background of a muscle disease discovered in Finland established

Helsinki University research helped develop a gene test for detecting the disease.

The genetic background of a muscle disease discovered in Finland has been established. Sini Penttilä, a molecular geneticist defending her doctoral dissertation at the University of Helsinki, established in her dissertation the genetic background of SMAJ, the Jokela type of spinal muscular atrophy, and found the mutation causing the disease. Based on these findings, a gene test carried out on a blood sample was developed for diagnosing the disease.

“The gene test developed for detecting the disease establishes the sequence of bases in the chromosomal location that causes the disease. This enables us to see whether the patient is carrying the pathogenic mutation,” says Penttilä.

Early detection of SMAJ reduces human suffering

In its early stages, SMAJ resembles the quickly progressing and terminal ALS, or amyotrophic lateral sclerosis, but SMAJ is a disorder of its own and significantly less severe than ALS. And yet, many SMAJ patients have at first received a crushing ALS diagnosis. The early detection of SMAJ is important in order to avoid those afflicted by the disease having to be unnecessarily afraid of a fatal disorder.

The disease onset occurs between ages 30 and 40, and it damages the lower motor neurons in the spinal cord. Initial symptoms include painful muscular cramps and twitching in all limbs. The muscles of the affected gradually weaken and atrophy, but the disease progresses slowly and those afflicted can, for example, continue walking for a long time after the first symptoms. The disease does not affect life span.

It is inherited by an autosomal dominant mechanism, which means that the children of SMAJ patients have a 50% risk of developing the disease.

“There is no cure for the disorder, but its detection is important for patients to receive an accurate prognosis and for physicians to be able to avoid inappropriate treatment,” says Penttilä.

Disease unique to Finns

For now, SMAJ has only been diagnosed in Finns. Originally, it was identified in two families living in eastern Finland. For research purposes, the entire genome of these families was mapped out, after which the disease was found to be connected with a certain chromosome region, known by the researchers as 22q11.2-q13.2. The disease cause was revealed to be a mutation in a single gene (CHCHD10), found in all SMAJ patients diagnosed so far. The investigation demonstrated that SMAJ is a genetically distinct disease.

SMAJ is particularly common in North Karelia, and patients are usually descendants of this region.

The disease has been categorised as part of the Finnish Disease Heritage. It is a relatively rare disease that only afflicts around 200 individuals in Finland. This, however, makes it a relatively common among neurological diseases, as well as one of the most prevalent diseases included in the Finnish Disease Heritage. The heritage comprises some forty rare diseases caused by a single gene mutation that occur more frequently in Finland than elsewhere. Among the disorders are eye diseases, diseases of the fetus and newborn infants, as well as growth disorders.

The official name of SMAJ is spinal muscular atrophy, Jokela type.

Sini Penttilä defended her doctoral dissertation "Genetic background of late-onset spinal motor neuronopathy" at the Faculty of Biological and Environmental Sciences, University of Helsinki in August 2018. She is working at the Neuromuscular Research Centre of the University of Tampere, where the study was also conducted.

Sini Penttilä