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Respiratory ciliopathies including non-CF bronchiectasis v5.4 CA12 Matthew Edwards gene: CA12 was added
gene: CA12 was added to Respiratory ciliopathies including non-CF bronchiectasis. Sources: Expert Review
Mode of inheritance for gene: CA12 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CA12 were set to PMID: 26911677; PMID: 35359895
Phenotypes for gene: CA12 were set to isolated hyperchlorhidrosis
Review for gene: CA12 was set to AMBER
Added comment: 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