Annals of Laboratory Medicine

Korean Society for Laboratory Medicine (대한진단검사의학회)
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Unique TTR Variants D38A and M13dup Among Korean Patients with Hereditary Transthyretin Amyloidosis: A Retrospective Single-Center Cohort Study

  • Min-Seung Park (Department of Laboratory Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine) ;
  • Jae Joon Lee (Department of Laboratory Medicine, Seegene Medical Foundation) ;
  • Darae Kim (Division of Cardiology, Department of Medicine, Heart Vascular Stroke Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Jin-Oh Choi (Division of Cardiology, Department of Medicine, Heart Vascular Stroke Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Seok Jin Kim (Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Kihyun Kim (Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Ju-Hong Min (Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Hyun-Young Kim (Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Hee-Jin Kim (Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine)
  • Received : 2025.05.07
  • Accepted : 2025.09.30
  • Published : 2026.05.01
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Abstract

Background: Transthyretin amyloidosis, a protein-misfolding disorder characterized by systemic amyloid deposition, can be classified as wild-type transthyretin amyloidosis (ATTRwt) or hereditary transthyretin amyloidosis (ATTRv), depending on the presence of transthyretin (TTR) gene variants. We examined the genetic distribution of TTR variants in Korean patients diagnosed with ATTRv. Methods: We retrospectively reviewed 801 participants who underwent TTR analysis at Samsung Medical Center from 2012 to 2024. The participants were categorized into two groups: in-house probands or relatives, and externally referred probands or relatives. Results: Pathogenic or likely pathogenic TTR variants were detected in 36 of 165 in-house probands (21.8%), among which D38A was the most frequent variant (50.0%; 18/36), followed by M13dup and E89K (8.3% each). Among referred probands, D38A was predominant (54.5%; 12/22), followed by M13dup (22.7%; 5/22). Cardiac amyloid involvement was the most common manifestation, observed in 97.2% (35/36) of in-house probands with ATTRv, followed by peripheral nervous system (PNS; 94.4%) and autonomic nervous system (ANS; 88.9%) involvement. In contrast, ANS involvement was most prevalent among in-house relatives who underwent organ evaluation (61.5%; 24/39), followed by cardiac (52.1%; 25/48) and PNS (48.7%; 19/39) involvement. Five of the eight in-house relatives harboring M13dup (62.5%) showed organ involvement, primarily in the ANS, supporting the pathogenicity of this variant. Conclusions: This study provides the largest single-institution dataset of Korean patients with ATTRv, incorporating systematic organ assessments. The predominance of the unique TTR variants D38A and M13dup delineates a distinct genetic landscape that may facilitate accurate and timely diagnosis of ATTRv in the Korean population.

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References

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