J Genet Med.  2020 Jun;17(1):51-54. 10.5734/JGM.2020.17.1.51.

Importance of family segregation in the American College of Medical Genetics and Genomics and Association of Molecular Pathology guidelines: Case of a Korean family with autosomal dominant polycystic disease

Affiliations
  • 1Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
  • 2Outpatient Nursing Team, Samsung Medical Center, Seoul, Korea

Abstract

Since the American College of Medical Genetics and Genomics and Association of Molecular Pathology published their guidelines in 2015, most interpretations of genetic tests have followed them. However, all variants have only limited evidence along 28 interpretation standards, especially de novo variants. When de novo variants, which are classified as variants of uncertain significance (VUS) due to lack of evidence, are detected, segregation in the affected family could provide an important key to clarifying the variants. Autosomal dominant polycystic kidney disease is the most common inherited kidney disorder with pathogenic variants in the PKD1 or PKD2 genes. We detected a novel in-frame deletion variant in the PKD1 gene, c.7575_7577del (p.(Cys2526del)), which was interpreted as a VUS. We analyzed this variant in a Korean family to decide for segregation. Here, we report the variant as a likely pathogenic variant based on the evidence of segregation in three affected relatives and two unaffected members.

Keyword

Autosomal dominant; Polycystic kidney; Polycystic kidney disease 1 protein
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