Genotype-Phenotype Correlation of a Rare Transthyretin Variant Causing Amyloidosis

Area of Science:

• Cardiology
• Neurology
• Genetics

Background:

• Left ventricular hypertrophy (LVH) is a common condition with diverse causes.
• Hereditary transthyretin amyloidosis (hATTR amyloidosis) is a progressive disease often associated with specific mutations.

Observation:

• A middle-aged woman presented with LVH and neuropathy.
• No family history or regional prevalence of hATTR amyloidosis was reported.
• Diagnostic workup revealed a rare transthyretin variant as the underlying cause.

Findings:

• The patient exhibited a mixed phenotype, combining cardiac (LVH) and neurological (neuropathy) manifestations.
• Genetic analysis identified a rare transthyretin variant previously not widely associated with this presentation.
• Clinical data supports the pathogenicity of this rare transthyretin variant in causing disease.

Implications:

• This case expands the known clinical spectrum of transthyretin variants.
• It underscores the importance of considering genetic testing for transthyretin variants in unexplained LVH and neuropathy.
• Early diagnosis and management of hATTR amyloidosis, even with rare variants, can improve patient outcomes.