Targeted syndrom under study
TUBA1B (602530 OMIM)
Variants in the genes of the tubulin superfamily are known to be associated with Tubulinopathies. This term encompasses a group of neurodevelopmental disorders typically characterized by the presence of dysmorphic basal ganglia, callosal hypodysgenesis, cerebellar hypoplasia/dysplasia and a range of malformations of cortical development on brain MRI. The most common mutated tubulin gene is the tubulin alpha-1A gene (TUBA1A), whereas its homologous TUBA1B has not been associated yet to a human phenotype.
TUBA1B encodes the tubulin α -1b, a protein of 451 amino acids including two functional domains, the Tubulin/Ftsz GTPase domain (3-213) and the Tubulin C terminal domain (263-391). Remarkably, TUBA1B shows a high degree of homology with TUBA1A, from which differs for only two amino acids.
We have assembled a cohort of more than 20 cases harboring de novo missense variants in TUBA1B. All affected individuals present with developmental delay / intellectual disability and brain malformations, which range from tubulinopathy spectrum to midline defects. Additional features include microcephaly and short stature. Interestingly some individuals display proximal intestinal atresia or duplication, congenital hypothyroidism, skeletal anomalies and hematological/immunological abnormalities.
Currently, we are performing functional studies in vitro and in vivo through a zebrafish model and we aim to expand the mutational and phenotypic spectrum of TUBA1B-related developmental disorder adding new patients to this ongoing study.
Contributing clinicians will be acknowledged as co-authors of a future publication.
Department of Human Genetics
McGill University Health Centre
Montreal, Quebec, Canada
Specific requirements beyond clinical data and genotype data sharing:
- Re-analysis of DNA samples: No
- Resampling of patients: No
- Linked to a translational/basic research project: No