Skip to main content

Conference Program

Subpage Hero

Loading

Enhanced Access to Genome Sequencing and the Era of Multiple Genetic Diagnoses: Advantages and Limitations 

Clinical Genetics and Therapeutics
  • Primary Categories:
    • Clinical Genetics
  • Secondary Categories:
    • Clinical Genetics
Introduction
     Clinical genome sequencing is becoming widely available. The advancement in genome sequencing technology has improved its diagnostic yield and opened more doors for prognostic and management insights. Moreover, genome sequencing cost it trending down, which helped to enhance its availability and access to many patients with complex medical history. We present a patient with complex medical history who was found to have four different confirmed genetic disorders.

 

Case Presentation
     Our patient came to medical attention at 31 years of age when she was diagnosed with hypertriglyceridemia during her routine health checkup. She was diagnosed with periodic fevers at 32 years of age. She experienced two episodes of idiopathic pancreatitis at 41 years of age and was found to have multiple hepatic adenomatosis (>30) at 46 years of age. She was diagnosed with primary hyperaldosteronism at 47 years of age. Her family history is positive for hyperaldosteronism in her father and recurrent fevers in her 20 years old daughter. Both parents were deceased at the time of genetic testing. H

Diagnostic Workup
er proband only genome sequencing showed multiple results as follows: 

  • Heterozygous for a pathogenic variant in CHEK2 gene (c.1011C>A;pTyr337Ter), confirming her diagnosis of autosomal dominant Tumor Predisposition Syndrome 4 Breast/Prostate/Colorectal

  • Heterozygous for a likely pathogenic variant in APOA5 gene (c.913C>T;p.Gln305Ter), confirming her diagnosis of autosomal dominant hypertriglyceridemia and late-onset hyperchylomicronemia.

  • Heterozygous for a pathogenic variant in RIPK1 gene (c.1934C>T:p.Thr645Met), confirming her diagnosis of autosomal dominant Autoinflammation with Episodic Fever and Lymphadenopathy.

  • Heterozygous for a deep intronic variant of uncertain significance in HNF1A gene (c.327-1445C>T). Transcriptome analysis confirmed that this variant results in abnormal splicing event, which supports its pathogenicity in causing hepatic adenomatosis. 




Treatment and Management
The patient is following with multidisciplinary team to evaluate and monitor her multiple genetic diagnoses including clinical genetics, hematology and oncology, endocrinology, rheumatology, gastroenterology, hepatology, and breast cancer. 

 

Conclusion
Genome sequencing is a valuable tool in clinical genetics. Its improved diagnostic yield and access has helped many patients to get a more comprehensive and individualized healthcare. Additionally, it highlights that multiple genetic diagnoses can be a common scenario in clinical practice. On the other hand, patients with multiple genetic diagnoses face unique medical, social, and psychological challenges. The enhanced access and advancement in genome sequencing calls for more resources to be directed toward multidisciplinary care clinics and centers. 

Agenda

Sponsors