Novel, likely pathogenic variant in ATP7A associated with Menkes disease diagnosed with ultrarapid genome sequencing

Area of Science:

• Genetics
• Neurodegenerative Diseases
• Biochemistry

Background:

• Menkes disease is a severe X-linked neurodegenerative disorder impacting copper metabolism.
• Clinical diagnosis is often delayed due to variable presentation and reliance on symptoms like kinky hair and developmental regression.
• The ATP7A gene is primarily implicated in Menkes disease.

Purpose of the Study:

• To highlight the potential of ultrarapid whole genome sequencing for timely Menkes disease diagnosis.
• To describe a case of Menkes disease diagnosed rapidly via whole genome sequencing.
• To emphasize the clinical manifestations and pathophysiology of Menkes disease.

Main Methods:

• Ultrarapid whole genome sequencing was employed for diagnosis.
• Genetic analysis focused on identifying variants in the ATP7A gene.
• Clinical data and pathophysiology were reviewed.

Main Results:

• A novel, likely pathogenic, frameshift variant in the ATP7A gene was identified.
• The genetic finding was consistent with a diagnosis of Menkes disease.
• Preliminary diagnostic results were obtained within hours.

Conclusions:

• Ultrarapid whole genome sequencing offers a significantly faster diagnostic pathway for Menkes disease compared to traditional methods.
• Early diagnosis through genetic sequencing can lead to earlier intervention and potentially improved patient outcomes.
• This case underscores the utility of advanced genomic technologies in diagnosing rare genetic disorders.