Researchers from VUmc and Amsterdam Neuroscience (Marjo van der Knaap and Nicole Wolf; Center for Children with White Matter Disorders) and a team in Australia together with colleagues in Canada have found a new gene for a genetic and severe brain disease in children. By sharing the data in a large international database, they also found another patient in Canada with this rare disease.
Hypomyelinating leukodystrophies are a heterogeneous group of disorders with a clinical presentation that often includes early-onset nystagmus, ataxia and spasticity and a wide range of severity. Using next-generation sequencing techniques and GeneMatcher, we identified four unrelated patients with brain hypomyelination, all with the same recurrent dominant mutation, c.754G>A p.(Asp252Asn), in TMEM106B. The mutation was confirmed as de novo in three of the cases, and the mildly affected father of the fourth affected individual was confirmed as mosaic for this variant. The protein encoded by TMEM106B is poorly characterized but is reported to have a role in regulation of lysosomal trafficking. Polymorphisms in TMEM106B are thought to modify disease onset in frontotemporal dementia, but its relation to myelination is not understood. Clinical presentation in three of the four patients is remarkably benign compared to other hypomyelinating disorders, with congenital nystagmus and mild motor delay. These findings add TMEM106B to the growing list of genes causing hypomyelinating disorders and emphasize the essential role lysosomes play in myelination.
Read the scientific article in Brain.
The Global Alliance for Genomics and Health (GA4GH) is a non-profit organization and aims to accelerate progress in genomic research and human health by cultivating a common framework of standards and harmonized approaches for effective and responsible genomic and health-related data sharing. This platform is accessible to doctors anywhere in the world. In Canada GA4GH made a video about the impact of the so-called 'gene-matching' and the resulting diagnosis on one of the families. Watch this video.