Absence of GJA1 gene mutations in four patients with anomalous left coronary artery from the pulmonary artery [ALCAPA]

ABSTRACT

Anomalous left coronary artery from the pulmonary artery [ALCAPA] is a rare form of congenital heart disease with no known genetic cause. It is usually diagnosed within the first year of life ; it results in myocardial cell death, congestive heart failure and lethality if left untreated. Connexin 43 alpha 1 is a member of the gap junction family of proteins demonstrated by animal studies to have a role in coronary artery patterning during development. No previous studies have investigated the role of this gene in patients with ALCAPA. We forth herein describe the clinical presentation of four patients who presented to the Children's Heart Center at AUBMC and had the final diagnosis of ALCAPA. Screening the GJA1 gene coding for connexin 43 alpha 1 was undertaken. No mutations were found in the patients or their parents, except for one polymorphism in one of the parents in the 3' untranslated region. All four patients underwent surgical repair with excellent outcome. This paper raises the awareness of this rare condition enabling physicians to reach the adequate diagnosis which will allow early surgical intervention and better prognosis. Our patient sample did not exhibit any evidence of association between connexin 43 alpha 1 and the clinical phenotype