Novel compound heterozygous variants in the PLD1 gene causing cardiac valve dysplasia 1 complicated with dilated cardiomyopathy: a case report.

OBJECTIVE: Congenital heart disease (CHD), the most common congenital defect, accounts for one-third of all congenital anomalies. Genetic causes are identified in 20%-30% of CHD cases, mostly involving abnormal valve formation. PLD1 gene variants are postnatally associated with pulmonary stenosis, valvular regurgitation, left ventricular dilation and right ventricular hypoplasia. METHODS: Clinical data of the proband were collected, and targeted capture high-throughput sequencing was performed on the proband and his family members. The detected gene variants were interpreted according to the ACMG guidelines, and the correlation between variants and diseases was analyzed by combining clinical phenotypes and genetic characteristics. RESULTS: The proband presented with recurrent fatigue, palpitations, and aggravated symptoms for 2 days, with a history of cardiac valve disease for more than 17 years and three open-heart surgeries. Echocardiography showed left ventricular enlargement, decreased ventricular wall motion amplitude, and mild tricuspid regurgitation. Genetic testing identified two novel compound heterozygous variants in the PLD1 gene: NM_002662.5: c.434 + 1G > T (a splice site variant, inherited from the father, classified as pathogenic) and NM_002662.5:c.2681A > G (a missense variant, NP_ 002653.1: p.Tyr894Cys, inherited from the mother, classified as a variant of uncertain significance). CONCLUSION: These two novel compound heterozygous variants in PLD1 may be the pathogenic genetic cause of cardiac valve dysplasia 1 (CVDD1) complicated with dilated cardiomyopathy (DCM) in this patient, which expands the variant spectrum of PLD1 and provides valuable evidence for genetic diagnosis and genetic counseling of CVDD1 and related cardiomyopathies.