Chromosome 10p15.3 is the most distal segment of 10p. The deletions within this area are characterized by developmental delay, motor skill delay, speech disorders, brain abnormalities, and seizures. Two genes within this region – ZMYND11 and DIP2C – are commonly deleted due to this condition, and loss of these is thought to contribute to some of the symptoms. Deletions in ZMYND11, in particular, have been connected to speech delay, language disorder, and developmental difficulties. Prior to the findings of these articles, not enough evidence was available to conclude that a loss of ZMYND11 is the main reason behind the symptoms mentioned above.
The Poluha et al. article presents a patient with a 1.08Mb deletion (which included ZMYND11) within the 10p15.3 region. The girl is the third child of a family with no previous history of intellectual disability or developmental issues. She was born in good condition, but her health deteriorated rapidly due to a congenital heart defect (found in a small portion of individuals with the 10p15.3 deletion). Her developmental milestones were delayed, and she displayed symptoms of mild epilepsy around the age of 3. Overall, her clinical symptoms (above heart defect) included developmental delay, motor delay, severe language impairment, dysmorphic features, hypotonia (low muscle tone), seizures and brain malformation (Chiari malformation type I).
Tumiene et al. reported 2 persons with the loss of the distal 10p15.3 segment caused by pericentric inversions of chromosome 10. They compared manifestations in their patients, several patients with 10p15.3 deletion from the literature and 8 patients with ZMYND11 loss-of-function mutations. The comparison showed remarkable similarities between patients with deletions and ZMYND11 mutations: intellectual disability, developmental delay, behavioral issues (including autism, ADHD, aggressiveness, and bipolar disorder), hypotonia, mild craniofacial dysmorphism, brain anomalies, seizures, and low birth weight were common in both groups.
Both Poluha et al. and Tumiene et al. suggest that ZMYND11 is the major gene involved in the symptoms of the 10p15.3 deletion.
ZMYND11 gene is considered to be important to the proper functioning of epigenetic regulation. Epigenetic regulation – which is a way of managing of the expression of genes – is critical for the proper development of the brain. Therefore, a number of brain abnormalities can be attributed to the loss of epigenetic regulation. This reasoning would explain why loss of ZMYND11 would cause the neurological symptoms of the 10p15.3 deletion.
Poluha et al. “Molecular and clinical characterization of new patient with 1.08 Mb deletion in 10p15.3 region”. Molecular Cytogenetics, 2017, v. 10: 34.
Tumiene et al. “Phenotype comparison confirms ZMYND11 as a critical gene for 10p15.3 microdeletion syndrome”. Journal of Applied Genetics, 2017, in press.