Scientists unravel genetic basis for neurodegenerative disorders that affect vision

May 21, 2024
NIH-led findings point to a biomarker for rare disorders associated with the gene PNPLA6.

Led by researchers at the National Institutes of Health (NIH), a team of scientists has uncovered the complex molecular mechanisms underlying neurodegenerative disorders linked to the gene PNPLA6, which encompass a range of conditions affecting mobility, vision, and hormonal regulation.

The research was published in the journal BRAIN.

Robert Hufnagel, M.D., Ph.D., and colleagues at the NIH’s National Eye Institute (NEI) Ophthalmic and Visual Function Branch, conducted a systematic review and analysis of data from more than 100 patients with PNPLA6 mutations. Using neuroimaging, electrophysiological studies (where neurons’ electrical signals are measured and analyzed to understand their function and properties), and genetic testing information, the researchers meticulously evaluated mobility, vision, and hormone expression.

Results revealed that symptom severity is driven by single substitutions in the DNA code “building blocks” or nucleotides – adenine (A), thymine (T), cytosine (C), and guanine (G), called missense mutations. Each combination of three letters (ATC, or TCG, for example) determines an amino acid, which is the basis of all proteins. When a missense variant occurs, it can affect how the protein functions, potentially leading to health issues.

How these mutations affect NTE function depends on where they occur in the PNPLA6 gene.  

NIH release