Abstract
INTRODUCTION: Truncus arteriosus (TA) is a life-threatening cardiovascular anomaly involving a ventricular septal defect and a common ventricular outflow tract. Recently, biallelic variants in TMEM260 have been identified as causative for structural heart defects and renal anomalies syndrome (SHDRA, MIM 617478), which includes TA. Approximately 30 patients with SHDRA have been reported, but the genotype-phenotype correlation remains unclear. Founder variants have been identified in patients of East Asian and Ashkenazi Jewish ancestry. CASE PRESENTATION: The male infant, the third child of unrelated Japanese parents, was prenatally diagnosed with TA via detailed ultrasound examination. His older sister also had TA and died at 20 days of age. Despite intensive cardiorespiratory care, the patient passed away at 53 days due to heart failure. Genetic analysis identified a homozygous deletion of TMEM260 exons 6 and 7, resulting from a 7,066-bp deletion with a 1 bp insertion, inherited from heterozygous parents. This deletion is included in the structural variation dataset with an allele frequency of 0.00173 (29/8,380) in ToMMo 8.3K JPN-SV. DISCUSSION: This is the first familial TA caused by a biallelic structural variation in TMEM260. The 7,066-bp deletion shows a high allele frequency in the Japanese population. These findings support the idea that this TMEM260 deletion may be a significant cause of TA and should therefore be considered alongside the previously known c.1617del variant as a potential causative factor.