Identification of BMP10 as a Novel Gene Contributing to Dilated Cardiomyopathy

Area of Science:

• Cardiology
• Genetics
• Molecular Biology

Background:

• Dilated cardiomyopathy (DCM) is a prevalent cardiac muscle disease causing heart failure and requiring heart transplantation.
• While genetic factors are implicated, many DCM-causing genes remain undiscovered, necessitating further research.
• Understanding the genetic basis of DCM is crucial for diagnosis and treatment.

Purpose of the Study:

• To identify novel genetic causes of dilated cardiomyopathy (DCM).
• To investigate the role of the BMP10 gene in autosomal-dominant DCM within a Chinese Han family.
• To elucidate the functional consequences of a novel BMP10 variant on gene regulation.

Main Methods:

• Whole-exome sequencing and Sanger sequencing were employed to analyze DNA from affected family members.
• A novel BMP10 variant (c.166C > T; p.(Gln56*)) was identified and its co-segregation with DCM phenotype was confirmed.
• Dual-luciferase reporter assays were performed to assess the functional impact of the mutant BMP10 on target gene transactivation.

Main Results:

• A novel heterozygous BMP10 variant, p.(Gln56*), was found to segregate with DCM in a multigenerational Chinese Han family.
• This BMP10 variant was absent in 268 healthy control subjects.
• The Gln56*-mutant BMP10 demonstrated impaired transactivation of known DCM-related genes, NKX2.5 and TBX20.

Conclusions:

• BMP10 is identified as a novel causative gene for dilated cardiomyopathy in humans.
• BMP10 haploinsufficiency emerges as a potential pathogenic mechanism in DCM.
• These findings may facilitate early genetic diagnosis and precision prophylaxis of DCM.