“We identified seven affected females in four pedigrees with likely pathogenic variants in ZNF142” – Khan et al. 2019
Several members of the Genetics of Stuttering team were involved in this study, recently published in Genetics in Medicine. This study does not explore the genetics of stuttering, instead it forms part of another project within the Centre of Research Excellence in Speech and Language, which examines the genetic causes of a severe speech disorder called Childhood Apraxia of Speech.
How did we find this gene?
We carried out whole exome sequencing in a child with apraxia of speech, and both of their parents, neither of whom had apraxia of speech. Whole exome sequencing is where we measure every base, specifically in the parts of each gene which code for proteins.
We found that the child had two very rare genetic variants in a gene called ZNF142. One of these variants was inherited from Mum, the other was inherited from Dad. We also looked at this gene in the child’s two siblings. Neither of the siblings shared this combination of genetic variants and neither had apraxia of speech. This seemed like a promising finding!
We then went to a website called GeneMatcher (a bit like a matchmaking site for geneticists!), where we got in touch with other scientists who were studying this gene. In addition to the child in our family, there were another six children from three different families who had variants in this gene, and also had neurodevelopmental problems.
What is the neurodevelopmental disorder caused by this gene?
The seven children all had slightly different neurodevelopmental problems, but common to all were cognitive problems, motor impairment and speech issues.
What does the gene do?
The ZNF142 gene codes for a Zinc Finger Protein. This protein is thought to help with controlling when and where some of our other genes are making proteins. ZNF142 hadn't been directly linked to any disease, prior to this study; however similar genes, which code for other Zinc Finger Proteins, are known to be involved in a number of conditions affecting the central nervous system.
Khan, K., Zech, M., Morgan, A. T., Amor, D. J., et al. (2019). Recessive variants in ZNF142 cause a complex neurodevelopmental disorder with intellectual disability, speech impairment, seizures, and dystonia. Genetics in Medicine, 1. https://doi.org/10.1038/s41436-019-0523-0