Welcome to the Gene Scene! Each week, we will explore a gene from the ACMG Secondary Findings list—genes identified by the American College of Medical Genetics and Genomics as having clear, actionable health implications. These genes are included because they’re linked to serious but preventable or manageable conditions when identified early. Here, we focus on the condition that led to the gene’s inclusion on the list, providing clear, relevant information that supports your clinic. To subscribe to the Gene Scene, contact your local GSL or send a request to info@ambrygen.com. 

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Clinical Phenotype Summary: 

The ENG gene is located on chromosome 9q34.11 and encodes the endoglin protein. Pathogenic variants in this gene are known to cause ENG-related hereditary hemorrhagic telangiectasia (HHT), also known as Osler-Weber-Rendu disease, which is inherited in an autosomal dominant fashion. Loss of function has been reported as the mechanism of disease for ENG-related hereditary hemorrhagic telangiectasia (HHT).

Diagnostic criteria for ENG-related HHT include:
     -    Recurrent epistaxis
     -    Mucocutaneous telangiectases
     -    Visceral arteriovenous malformations (particularly pulmonary and cerebral types)
     -    Family history of HHT 
Other features include: 
     -    Anemia, which may require iron replacement therapy or transfusion
     -    Pulmonary hypertension (in rare cases)
HHT displays age-related penetrance with increased manifestations developing over an individual’s lifetime (McAllister, 1994; Kritharis, 2018; Kilian, 2020). 

Clinical Resources: 
Understanding Your Result: HHT Positive

Ambry Knows Genes: 
Webinar: Advanced LearnENG: A Clinical and Diagnostic Update for HHT

Citations: 
-    McAllister KA et al, Nature genetics 1994 Dec; 8(4):345-51 PMID: 7894484
-    Kritharis A, et al, Haematologica 2018 Sep; 103(9):1433-1443 PMID: 29794143
-    Kilian A et al, Journal of clinical medicine 2020 Aug; 9(9) PMID: 32842615
-    Ambry Genetics Gene-Disease Validity Scheme

Each week, we explore a gene from the ACMG Secondary Findings list—genes identified by the American College of Medical Genetics and Genomics as having clear, actionable health implications. These genes are included because they’re linked to serious but preventable or manageable conditions when identified early. 

To learn more about the ACMG Secondary Findings list, click here.