NKAP gene mutation linked to rare developmental disease

Researchers have identified a gene mutation that causes developmental delay, behavioural abnormalities and musculoskeletal problems in children. The team believe that this discovery could lead to therapeutic strategies to combat NKAP-related syndrome.

The study was conducted at the Children’s Hospital of Philadelphia, US. The researchers revealed how mutations to the NKAP gene disrupts transcription, when DNA is converted into RNA.

Performing exome sequencing on 10 patients, all children and young adults with the symptoms, the researchers identified the mutation on the X chromosome. As the NKAP mutation is consistent with an X-linked recessive condition, only males display the phenotype.

Further examination revealed that transcription disruption patterns were similar in the patients; a higher proportion of genes were downregulated than upregulated. In zebrafish models, the team showed there were similar effects from an analogous mutated gene.

“As my lab continues to explore the function of NKAP in our bodies, we aim to discover clues for future treatments,” said study leader Dr Kosuke Izumi, MD, a clinical geneticist and genetics researcher at Children’s Hospital of Philadelphia.

The team have also initiated a registry to collect clinical information on patients with the condition. According to the researchers, investigating the biological mechanisms of this syndrome may allow them to discover a molecular pathway to target in future treatments.  

The findings were published in the American Journal of Human Genetics.