Renal amyloidosis caused by apolipoprotein A-II without a genetic mutation in the coding sequence

Area of Science:

• Nephrology
• Genetics
• Pathology

Background:

• Renal amyloidosis is typically caused by acquired light-chain or reactive systemic amyloid A.
• Hereditary amyloidosis, including apolipoprotein A-II (apoAII) amyloidosis, is less common and often undiagnosed.
• A genetic mutation in the apoAII stop codon is the presumed cause of apoAII amyloidosis.

Observation:

• A 68-year-old man presented with progressive proteinuria (6 g/day) over one year.
• Renal biopsy revealed amyloid deposition in glomeruli, excluding common causes.
• Immunohistochemistry confirmed apoAII deposition, but genetic sequencing found no mutations in the apoAII coding sequence.

Findings:

• This case describes apoAII amyloidosis in a patient lacking a family history and identifiable genetic mutation in the apoAII coding sequence.
• The findings suggest potential non-coding sequence mutations or other genetic mechanisms contributing to apoAII amyloid fibril formation.

Implications:

• The study expands the understanding of apoAII amyloidosis etiology beyond known coding sequence mutations.
• Further investigation is warranted to elucidate the full spectrum of genetic factors and diagnostic pathways for apoAII amyloidosis.
• This case underscores the importance of considering rare hereditary forms of amyloidosis even in the absence of typical genetic markers.