Approaching patients with a ‘genotype-first’ technique could help us to better understand genetic diseases and to develop faster, more accurate diagnostics, according to new research. The work, led by Gholson Lyon, MD, PhD, at Cold Spring Harbor Laboratory, involved using genomic data to identify a novel gene variant linked to intellectual disabilities. The research was published in The American Journal of Human Genetics last week.

These are genetic pedigrees of 3 families with individuals with familial or de novo (spontaneous) mutations in the NAA15 gene. The mutations caused different impacts (called phenotypes by scientists) in each of the affected individuals. So far, 37 individuals in 32 families have been found to have the newly identified illness. Source: Lyon Lab, CSHL

Ogden syndrome is a serious, X-linked developmental condition caused by a mutation in the NAA10 gene that was first identified by Dr Lyon’s team in 2011. Since then, the team has been studying the disease, in particular the NAA15 gene that produces a protein that works alongside the NAA10 gene during NatA-mediated N-terminal acetylation.

As part of this research Dr Lyon and his team have been collecting data from patients that carried a NAA15 mutation, identifying 37 male and female individuals from 32 families around the world.

“Trying to prove the relevance of any mutation in a gene requires a large number of samples,” Dr Lyon said. “As a result, we’re seeing the field of human genetics move more toward this type of large-scale collaboration.

“As the price of genetic sequencing drops and more people are sequenced, we may be able to provide individuals with such mutations with more education and services in early life which could lead to better overall functioning.”

The success of this type of approach indicates that a greater focus on a patient’s genotype instead of symptom-based diagnostics could improve our understanding of diseases.

“Instead of lumping many diseases together under very broad categories like ‘intellectual disability’ or ‘autism,’ the human genetics community is now splitting these into much finer entities so that we can begin to do natural history studies, much like what has been done with Fragile X syndrome,” Dr Lyon said.