Skip to Content
800-533-8762
  • Careers
  • Newsroom
  • Health Care Professionals
  • About Us
  • Contact Us
UPMC
  • Find a Doctor
  • Services
    • Frequently Searched Services
    • Frequently Searched Services
      Allergy & Immunology Behavioral & Mental Health Cancer Ear, Nose & Throat Endocrinology Gastroenterology Heart & Vascular Imaging Neurosciences Orthopaedics
      Physical Rehabilitation Plastic & Reconstructive Surgery Primary Care Senior Services Sports Medicine Telemedicine Transplant Surgery Walk-In Care Weight Management Women’s Health
      See all Services
    • Services by Region
    • Find a UPMC health care facility close to you quickly by browsing by region.
      UPMC in Western Pa. Western Pa. and New York
      UPMC in Central Pa. Central Pa.
      UPMC in North Central Pa. North Central Pa.
      UPMC in Western Md. Maryland & West Virginia
    • See All Services
  • Locations
    • Locations by Type
    • Locations by Type
      UPMC hospitals
      Hospitals
      Physical Therapy
      Physical Therapy
      Urgent care
      Walk-In Care
      UPMC Outpatient Centers
      Outpatient Centers
      UPMC Imaging Services
      Imaging
      Community Health Centers
      Community Health Centers
      See All Locations
    • Locations by Region
    • Locations by Region
      UPMC in Southwest Pa. Southwest Pa.
      UPMC in North Central Pa. North Central Pa.
      UPMC in Northwest Pa and Ny. Northwest Pa. & Western N.Y.
      UPMC in West Central Pa. West Central Pa.
      UPMC in Central Pa. Central Pa.
      UPMC in Western Md. Maryland & West Virginia
    • See All Locations
  • Patients & Visitors
    • Patient & Visitor Resources
    • Patient & Visitor Resources
      Patients and Visitors Resources Pay a Bill Classes & Events Medical Records Health Library Patient Information
      Patient Portals Privacy Information Shared Decision Making Traveling Patients Visitor Information
      Man uses mobile phone
      Pay a Bill
      Nurse reviews medical chart
      Request Medical Records
  • Patient Portals
  • Find Covid-19 updates
  • Schedule an appointment
  • Request medical records
  • Pay a bill
  • Learn about financial assistance
  • Find classes & events
  • Send a patient an eCard
  • Make a donation
  • Volunteer
  • Read HealthBeat blog
  • Explore UPMC Careers
Skip to Content
UPMC
  • Patient Portals
  • For Patients & Visitors
    • Find a Doctor
    • Locations
    • Patient & Visitor Resources
    • Pay a Bill
    • Services
    • More
      • Medical Records
      • Financial Assistance
      • Classes & Events
      • HealthBeat Blog
      • Health Library
  • About UPMC
    • Why UPMC
    • Facts & Stats
    • Supply Chain Management
    • Community Commitment
    • More
      • Financials
      • Support UPMC
      • UPMC Apps
      • UPMC Enterprises
      • UPMC International
  • For Health Care Professionals
    • Physician Information
    • Resources
    • Education & Training
    • Departments
    • Credentialing
  • Careers
  • Contact Us
  • Newsroom
  • UPMC >
  • Media Relations >
  • News Releases >
  • hlhs nature genetics
Media Relations
News Releases
Central Pa. News
North Central Pa. News
Contact Us
Experts
Community-Focused News
Media Kits
Media RSS
Media Relations
News Releases
Central Pa. News
North Central Pa. News
Contact Us
Experts
Community-Focused News
Media Kits
Media RSS

Chat Keywords List

  • cancel or exit: Stops your conversation
  • start over: Restarts your current scenario
  • help: Shows what this bot can do
  • terms: Shows terms of use and privacy statement
  • feedback: Give us feedback
Continue
Chat with UPMC
RESTART
MENU
CLOSE

​Genes Responsible for Severe Congenital Heart Disease Identified by Pitt Researchers

For Journalists

Gloria Kreps
Vice President
412-586-9764
krepsga@upmc.edu

Want to Make an Appointment or Need Patient Information?
Contact UPMC at

1-800-533-8762.

Go to Find a Doctor to search for a UPMC doctor.

University of Pittsburgh Schools of the Health Sciences

5/22/2017

Main Content
PITTSBURGH, May 22, 2017 – The first known identification of two genes responsible for hypoplastic left heart syndrome (HLHS), a severe congenital heart defect, has been reported by researchers at the University of Pittsburgh School of Medicine. The findings are published today in the journal Nature Genetics.
 
Congenital heart disease, or structural abnormalities in the heart that are present at birth, affect up to 1 percent of all live births. HLHS is a rare congenital heart disease where the left side of the heart is poorly developed, resulting in an inability to effectively pump blood to the rest of the body. It occurs in about 2 to 3 of every 10,000 live births in the United States, and is fatal if left untreated.
 
Current treatment for HLHS involves multiple complex surgeries in the first few years of a child’s life, and while effective in many patients, it does not improve heart function in many others. In those individuals, heart failure ensues and heart transplantation is required. The five-year survival rate for HLHS patients is approximately 50 to 70 percent.
 
Though genetic risk factors are known to play a role in HLHS, specific genes have been hard to identify.
 
“Studying diseases with complex genetics is extremely challenging. Our study has been made possible by leveraging findings from a large-scale analysis in mice to recover mutations causing congenital heart defects. This resulted in the recovery of the first mouse models of HLHS. Analysis of these mice with HLHS allowed us to identify for the first time two genes interacting in combination to cause HLHS,” said Cecilia Lo, Ph.D., professor at Pitt’s School of Medicine who also holds the F. Sargent Cheever Chair in Developmental Biology. “By understanding the genetics and biology of HLHS, this can facilitate development of new therapies to improve the prognosis for these patients.”
 
Lo and her team used fetal ultrasound imaging to screen mice with experimentally induced mutations, looking for structural heart defects. From this screen, they recovered eight different mouse strains with structural and functional heart defects indicative of HLHS.
 
By comparing the genome of mice with the HLHS heart defects to the genome of normal mice, Lo and her team identified several hundred mutations in the HLHS mutant strains. Further analysis of these mutant mice indicated the genetic origins of HLHS likely involve many interacting genes. The relevance of these mutations was reinforced by the fact that many also were found in the same chromosomal regions previously shown to be associated with HLHS from human genetic studies.
 
In one mouse strain, they discovered that mutations in two genes, named Sap130 and Pcdha9, were required for HLHS. “Interestingly, HLHS was found only in animals with mutations in both genes. However, animals that had mutations with Pcdha9, but not Sap130, can display defects in the aorta, but with normal-sized left ventricles, suggesting interaction between the two genes is needed to cause all the features of HLHS,” said Xiaoqin Liu, M.D., Ph.D., the first author of the new study and a research instructor in Lo’s lab.
 
Using CRISPR-Cas9 gene editing in mice, the researchers confirmed that mutations in these two genes can cause HLHS. Additionally, they sequenced 68 HLHS patient samples and found one individual with rare mutations in both SAP130 and PCDHA genes.
 
Molecular analysis showed that heart cells in affected animals were poorly developed and had mitochondrial defects, indicating that Sap130–Pcdha9 gene interactions play a crucial role not only in heart development but also in regulating metabolic function of the cardiac muscle.
 
These findings suggest HLHS may be associated with a fundamental cellular defect in the heart muscle that can compromise blood flow in patients. This has important therapeutic implications, as surgical repair will not be able to address the cellular muscle defect in HLHS patients, noted Lo. 
 
The researchers are investigating other mutations identified through the genetic screen and plan to undertake more genetic analysis of HLHS patients to better understand the molecular and genetic factors that cause the disease.
 
Other study authors included researchers from Pitt, The Jackson Laboratory, University of Rochester School of Medicine and Dentistry, Cincinnati Children’s Hospital Medical Center, Children’s National Medical Center, Boston Children’s Hospital, University of San Diego School of Medicine and Medical College of Wisconsin.
 
The study was supported by National Institutes of Health grants U01-HL098180, R01-HL132024, R01-GM104412, S10-OD010340, R01-MH094564, OD011185, the Children’s Heart Foundation, and the Junior Cooperative Society.

Heart of CRISPR gene edited mice with HLHS (bottom) have a much smaller left ventricle (LV) compared to a normal mouse heart (top). Right ventricle (RV), Aorta (AO).


Vidoemicroscopy of mouse fetus with HLHS showing robust contractile motion and blood flow from the right ventricle (RV), while the left ventricle (LV) is very small and exhibits only very weak contraction and no blood flow. Watch the related video.

Credit both: University of Pittsburgh/ Nature Genetics

UPMC
200 Lothrop Street Pittsburgh, PA 15213

412-647-8762 800-533-8762

Patients And Visitors
  • Find a Doctor
  • Locations
  • Pay a Bill
  • Patient & Visitor Resources
  • Disabilities Resource Center
  • Services
  • Medical Records
  • No Surprises Act
  • Price Transparency
  • Financial Assistance
  • Classes & Events
  • Health Library
Health Care Professionals
  • Physician Information
  • Resources
  • Education & Training
  • Departments
  • Credentialing
Newsroom
  • Newsroom Home
  • Inside Life Changing Medicine Blog
  • News Releases
About
  • Why UPMC
  • Facts & Stats
  • Supply Chain Management
  • Community Commitment
  • Financials
  • Supporting UPMC
  • HealthBeat Blog
  • UPMC Apps
  • UPMC Enterprises
  • UPMC Health Plan
  • UPMC International
  • Nondiscrimination Policy
Life changing is...
Follow UPMC
  • Contact Us
  • Website/Email Terms of Use
  • Medical Advice Disclaimer
  • Privacy Information
  • Active Privacy Alerts
  • Sitemap
© 2025 UPMC I Affiliated with the University of Pittsburgh Schools of the Health Sciences Supplemental content provided by Healthwise, Incorporated. To learn more, visit healthwise.org
Find Care
Providers
Video Visit
Portal Login