One of the most common primary cardiac arrhythmia syndromes is autosomal dominant long QT syndrome, type 1 (LQT1), chiefly caused by mono-allelic mutations in the javax.xml.bind.JAXBElement@1ece3341 gene. Bi-allelic mutations in the javax.xml.bind.JAXBElement@7269232c gene are causal to Jervell and Lange-Nielsen syndrome (JLNS), characterized by severe and early-onset arrhythmias with prolonged QTc interval on surface ECG and sensorineural deafness. Occasionally, bi-allelic mutations in javax.xml.bind.JAXBElement@2001e7dc are also found in patients without any deafness, referred to as autosomal recessive long QT syndrome, type 1 (AR LQT1).
We used Sanger sequencing to detect the pathogenic mutations in javax.xml.bind.JAXBElement@4f6526ea gene in eight families from Saudi Arabia with autosomal recessive LQT1.
We have detected pathogenic mutations in all eight families, two of the mutations are founder mutations, which are c.387-5T>A and p.Val172Met/p.Arg293Cys ( javax.xml.bind.JAXBElement@205e407c ). QTc and cardiac phenotype was found to be pronounced in all the probands comparable to the cardiac phenotype in JLNS patients. Heterozygous carriers for these mutations did not exhibit any clinical phenotype, but a significant number of them have sinus bradycardia.
To the best of our knowledge, this is the first description of a large series of patients with familial autosomal recessive LQT, type 1. These mutations could be used for targeted screening in cardiac arrhythmia patients in Saudi Arabia and in people of Arabic ancestry.