Hypomyelination with brainstem and spinal cord involvement and leg spasticity (HBSL) – DARS gene

Hypomyelination with brainstem and spinal cord involvement and leg spasticity (HBSL), also known as mitochondrial aspartyl-tRNA synthetase deficiency, is a type of leukodystrophy that affects the Central Nervous System. Specifically, this alteration affects the pyramidal tract, the lateral corticospinal tract and the dorsal spine, and is characterized in that the nervous system has a reduced capacity to form myelin.

This process is due to mutations in the DARS gene (aspartyl-tRNA synthetase), located on the long arm of chromosome 2 (2q21.3), which encodes the enzyme aspartyl-tRNA synthetase. This enzyme is found in all cell types and plays an important role in protein synthesis. Amino acids bind together in a specific order during protein synthesis, creating a chain of amino acids. The enzyme aspartyl-tRNA synthetase binds the amino acid aspartate to the corresponding tRNA, allowing aspartate to be added in the right place in proteins.

At least 16 mutations in the DARS gene have been identified that can lead to the development of HBSL. Most of the mutations described change individual amino acids in the enzyme aspartyl-tRNA synthetase. These alterations occur in a region of the enzyme called the active site, where aspartate and tRNA bind so that the amino acid can be transferred. The altered enzyme has difficulty adding the amino acid to tRNA, which in turn makes it difficult to add aspartate to proteins. It is not clear how the identified genetic mutations give rise to the signs and symptoms of HBSL.

This process is inherited with an autosomal recessive pattern, that is, both copies of the gene in each cell must have mutations for the alteration to be expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually do not show signs and symptoms of the disease.

Tests performed in IVAMI: in IVAMI we perform the detection of mutations associated with hypomyelination with brainstem and spinal cord involvement and leg spasticity (HBSL), by means of the complete PCR amplification of the exons of the DARS gene, and their subsequent sequencing.

Recommended samples: non-coagulated blood obtained with EDTA for separation of blood leukocytes, or a card with a dried blood sample (IVAMI can mail the card to deposit the blood sample).