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Unraveling the Genetic Basis of Congenital Diaphragmatic Hernia

Rady Children’s Hospital-San Diego is pioneering research into congenital diaphragmatic hernia (CDH), a challenging pediatric condition.


The underlying mechanisms of CDH have remained elusive, hindering effective treatments, but recent discoveries are paving the way for patient-specific therapies.

Breakthrough Research on Sin3a

Led by Dr. David McCulley, researchers identified loss-of-function mutations in the Sin3a gene as a key factor in CDH development. Whole-genome sequencing of patients with CDH revealed small deletions in Sin3a, disrupting diaphragm and lung development. Mouse models confirmed that Sin3a mutations lead to CDH-like features, including lung hypoplasia and pulmonary hypertension.

During development, Sin3a plays critical roles in organogenesis and cell lineage specification. Loss of Sin3a was found to impair energy metabolism and cell cycling, emphasizing its importance in normal embryonic growth and lung homeostasis.

Promising Therapeutic Discoveries

The study also demonstrated that partial inhibition of histone acetylation using anacardic acid improved lung development and pulmonary vascular function in Sin3a mutant mice. By restoring histone acetylation balance, this approach mitigated DNA damage, promoted cell proliferation, and reduced the severity of CDH-associated features.

“These findings have significant implications for clinical management,” said Dr. McCulley. “By understanding the molecular mechanisms of CDH, we can develop therapies tailored to individual patients, addressing unique genetic and epigenetic factors.”

Comprehensive CDH Care at Rady Children’s

Rady Children’s Comprehensive Congenital Diaphragmatic Hernia Center provides advanced care for infants and children with CDH. As part of its top-ranked Neonatology program, the center combines cutting-edge research with personalized treatment, supported by a multidisciplinary team.

To learn more, visit the Comprehensive CDH Center or explore the full study in Science Translational Medicine.

Learn more about Dr. David McCulley