Abstract
BACKGROUND/OBJECTIVES: The microtubule-associated scaffold protein 1 (MTUS1) gene affects the microtubule stability and cell polarity in the heart and could thus lead to the development of left ventricular noncompaction (LVNC). Pathological gene variants in MTUS1 are associated with pathological phenotypes in both cell cultures and animal models. However, the literature lacks human studies on the specific effects of the MTUS1 gene in heart disease, particularly in congenital LVNC. METHODS: We present a case of a male infant, diagnosed with LVNC, who passed away at the age of 8 months due to end-stage heart failure. In the investigation process of the etiology of LVNC, whole-genome sequencing using next-generation sequencing was performed in the patient and his first-degree family members. RESULTS: Genetic analysis identified two heterozygous variants in the MTUS1 gene (NM_001363059.2:c.87C>G and NM_001363059.2:c.2449+421_2288-425del) in the presented patient. The first variant introduced an early stop codon, while the second caused the deletion of an entire exon, both of which significantly altered the protein structure. The older brother of the patient, at the age of 5 years, was a carrier of both variants; however, he was asymptomatic and without signs of heart disease on cardiac ultrasonography. CONCLUSIONS: Although, in theory, defects in the MTUS1 gene may contribute to the development of LVNC, our observations indicate that MTUS1 variants alone are not sufficient to cause LVNC or lead to any significant developmental disorder. Additional factors, whether genetic or environmental, are likely necessary for the clinical manifestation of LVNC.