Clinical Reasoning: A 31-Year-Old Man With Sequential Vision Loss.

Area of Science:

• Genetics
• Ophthalmology
• Neurology

Background:

• Leber hereditary optic neuropathy (LHON) is a mitochondrial disease causing vision loss.
• Primary genetic testing often misses rare LHON mutations.
• Diagnosis can be challenging with initial negative results.

Purpose of the Study:

• To report a case of LHON diagnosed via mitochondrial whole-genome sequencing.
• To emphasize the utility of comprehensive genetic testing in suspected LHON cases.

Main Methods:

• Clinical presentation of painless sequential vision loss.
• Exclusion of infectious, inflammatory, and nutritional causes.
• Negative targeted genetic testing for common LHON mutations.
• Mitochondrial whole-genome sequencing (mtWGS).

Main Results:

• mtWGS identified a novel mutation at the 13513G>A position.
• This mutation confirmed the diagnosis of LHON.
• Standard treatments were ineffective, indicating a genetic basis.

Conclusions:

• Mitochondrial whole-genome sequencing is crucial for diagnosing LHON when primary mutation screening is negative.
• Rare mutations should be considered in LHON diagnosis.
• Early and accurate diagnosis is vital for patient management.