A previously unknown mutation in the BICD2 gene caused juvenile amyotrophic lateral sclerosis (ALS) in a Chinese woman in her 20s, according to a case study.
The gene had previously been linked to other neurodegenerative conditions, prompting researchers to believe that the mutation can give rise to ALS when other genetic or environmental factors are present.
The study, “A novel mutation of BICD2 gene associated with juvenile amyotrophic lateral sclerosis,” was published in the journal Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration.
The woman sought care at Peking University Third Hospital for progressive speaking difficulties, mild swallowing problems, and excessive saliva production.
After the initial examinations, the woman developed fits of forced laughter and crying, and was mildly stiff in her limbs. She did not have muscle weakness or wasting, but over the course of three years, it became increasingly difficult for her to walk.
Brain scans and metabolic tests were normal. Her symptoms were indicative of upper motor neuron disease, and first appeared to be hereditary spastic paraplegia.
Because electrophysiological nerve conduction tests indicated that ALS was the probable cause of her illness, researchers performed genetic tests. They also tested her for other diseases, such as hereditary spastic paraplegia and Charcot-Marie-Tooth disease, a type of muscular dystrophy.
Next generation sequencing revealed that the woman carried a mutation in the BICD2 gene. The change in a single DNA base led to another amino acid being incorporated into the protein, researchers said.
Further analyses showed that her mother carried the same mutation, without experiencing any symptoms. Running the mutation through software that can predict whether a mutation causes a disease yielded inconclusive results. One software program flagged the mutation as disease-causing, while another did not.
The BICD2 gene has been associated with other neuromuscular conditions. It was first linked to spinal muscular atrophy (SMA), but has since been found in patients with both upper and lower motor neuron disease.
The mutation is rare. Before it turned up in the woman with ALS, it had never been found in screenings or databases of genes in the Chinese population.
Since the gene has been linked to different types of motor neuron disease, the team concluded that the girl’s mutation can cause such a disease, but its development is likely dependent on other factors, genetic or environmental. The mutation in the unaffected mother supports this idea, the researchers said.