Lee et al. (2016) described a consanguineous Omani family with two children affected by elevated sweat chloride, infantile FTT, recurrent hyponatremia and bilateral hyperkeratosis of the heels. Genetic analysis identified a novel homozygous c.363C>A mutation in exon 4 of the CA12 gene of both patients. It segregated in an autosomal recessive pattern in the family and was predicted to result in a p.His121Gln substitution. Studies of the mutation along with a previously reported p.Glu143Lys variant found that while they did not affect CA12 protein localization, they resulted in a near complete loss of enzyme activity at physiologic concentrations of extracellular chloride. CA12 deleterious variants were also identified in a 25-year-old Caucasian female with elevated sweat chloride and pulmonary airway disease. Hence, while spirometry and chest X-rays of the Omani proband were normal, it was suggested that bronchiectasis might be present but was undetected due to lack of CT-scan analysis. This study highlighted the importance of screening for CA12 mutations in individuals that have CF-like features in the sweat gland and lung but no CFTR mutations.