The Gene Scene: TGFBR1

Bradley Power, MS, CGC
August 5th, 2025

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.

To access the Gene Scene archives, visit our blog.

Clinical Phenotype Summary:

The TGFBR1 gene (NM_004612.2), which contains 9 coding exons and is located on chromosome 9q22.33, encodes the TGF-beta receptor type-1. Pathogenic variants in this gene are known to cause TGFBR1-related Loeys-Dietz syndrome (LDS), which is inherited in an autosomal dominant fashion, and susceptibility to multiple self-healing squamous epithelioma (MSSE), which is also inherited in an autosomal dominant fashion.

TGFBR1-related LDS is characterized by:
•   Aortic aneurysm and/or
•   Early dissection with increased tortuosity of the aorta and major blood vessels
•   Bifid uvula
•   Cleft palate
•   Hypertelorism
•   Malar hypoplasia
•   Retrognathia
•   Arachnodactyly
•   Pectus deformity
•   Scoliosis

Intrafamilial clinical variability has been described, and rare examples of nonpenetrance in LDS have been documented. Mechanism of disease is unclear for TGFBR1-related LDS, but loss of function has not been suggested.

Susceptibility to MSSE is characterized by an increased risk of developing multiple skin tumors that spontaneously regress, leaving pitted scarring, particularly on the face and limbs. Age of onset and degree of severity are variable. Loss of function has been reported as the mechanism of disease for susceptibility to multiple self-healing squamous epithelioma.

Clinical Resources:

Understanding your Positive Thoracic Aortic Aneurysms/Dissections (TAAD) Results

Citations:
•   Loeys BL et al. N Engl J Med, 2006 Aug;355:788-98 PMID:16928994
•   Malyuk DF et al. Radiol Case Rep, 2022 Mar;17:767-770 PMID:35003478
•   Goudie D. Genes (Basel), 2020 11;11 PMID:33256177
•   Fujiwara T et al. Circ Rep, 2019 Nov;1:487-492 PMID:33693090

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.

Find Answers & Improve Patient Care

Ambry is committed to delivering the most accurate genetic test results possible. Learn more about our products today.

Contact A Sales Rep

Love this article?

Get stories just like it, delivered right to your inbox.

Author

Bradley Power, MS, CGC

Brad Power is a genetic counselor based in Irvine, CA, but he grew up on the east coast, just outside of Baltimore, MD. Brad first stepped into genetics studying bacterial genomics as part of his biology degree at St. Mary’s College of Maryland. From there he transitioned to human genetics and worked at the National Institutes of Health researching oculocutaneous albinism. Following his time in lab, he moved to Houston, TX to pursue his Masters in Genetic Counseling at the University of Texas Health Science Center. He returned to work as a genetic counselor at the NIH’s Undiagnosed Diseases Program and later worked in oncology at MD Anderson Cancer Center. Following his time in clinic, he transitioned to Ambry Genetics where he works as a genomic science liaison supporting cardiology, neurology and rare disease testing in Southern California and the Pacific Northwest.

DISCLAIMER: THIS BLOG DOES NOT PROVIDE MEDICAL ADVICE

The information, including but not limited to, text, graphics, images and other material contained on this blog are for informational purposes only. The purpose of this blog is to promote broad understanding and knowledge of various health topics. It is not intended to be a substitute for professional medical advice, diagnosis or treatment. Always seek the advice of your physician or other qualified health care provider with any questions you may have regarding a medical condition or treatment and before undertaking a new health care regimen, and never disregard professional medical advice or delay in seeking it because of something you have read on this blog. Ambry Genetics Corporation does not recommend or endorse any specific tests, physicians, products, procedures, opinions or other information that may be mentioned on this blog. Reliance on any information appearing on this blog is solely at your own risk.