Respiratory ciliopathies including non-CF bronchiectasis

Gene: CA12

I don't know

Gene confirmed to cause isolated hyperchlorhidrosis (OMIM#143860), which has been reported to mimic atypical Cystic Fibrosis (CF) - can cause elevated sweat chloride. Some variants associated with gene only cause isolated hyperchlorhidrosis, with no lung involvement, but some associated with broader hentypic spectrum affecting respiratory tract: BESC1 (Bronchiectasis with or without elevated sweat chloride 1). PMID: 26911677 describe two unrelated pedigrees with bi-allelic LOF variants in CA12. One proband: failure to thrive at 2-3 months of age, with sweat chlorides of 82-88mEq/L, with patient mis-diagnosed as having CF rising to 112-16 mEq/L at 9 years of age in one proband. Other phenotypic features: persistent cough, pseudomonas cultures. Other proband: presented at 6 years of age with a history of hyponatremic dehydration and elevated sweat chloride (90-110 mEq/L), with his sister showing a swet chloride of 130mEq/L (iin second pedigree though, there was no lung phenotype). Both sibs were homozygous for a novel missense variant.

Obviously limited evidence for patients with lung phenotype currently, but gene should be considered for panel as possible differential in ?CF patients with no CFTR variants detected.
Sources: Expert Review

Created: 21 Sep 2026, 1:05 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
isolated hyperchlorhidrosis

Publications

• PMID: 26911677
• PMID: 35359895