Respiratory ciliopathies including non-CF bronchiectasis

Gene: DNAH1

Red List (low evidence)

The ClinGen Motile Ciliopathy expert panel has classified the association of autosomal recessive DNAH1 variants to ciliary dyskinesia, primary, 37 (MONDO:0033204) as 'Limited'. More information can be found in https://search.clinicalgenome.org/CCID:004667.

As per ClinGen, three unrelated patients have been reported with DNAH1 variants and bronchiectasis and other respiratory phenotypes including cough and respiratory distress. However, one of these patients has been reported with heterozygous variants.

PMID:25927852 - Two affected sisters with PCD were identified with homozygous missense p.Lys1154Gln variant. The variant segregated with the phenotypes and was not found in unaffected members of the family. The proband had a history of chronic rhinitis, frequent coughing and wheezing, nasal discharge, and was diagnosed with left lung bronchitis. She also showed situs inversus and bronchiectasis, in addition to infertility.

PMID:31765523 - In a cohort of 265 patients with PCD, one patient was reported with heterozygous missense DNAH1 variant (p.Ala2599Ser).

PMID:34210339 - In a cohort of 26 individuals with PCD, one patient was reported with homozygous DNAH1 variant (p.P3909Rfs*33). The patient was infertile and presented with bronchiectasis, cough and sinusitis. As per ClinGen, this variant is recurrent in patients with isolated infertility and hence the association with PCD is doubtful.

Hence, this gene should be rated red with the current evidence.

Created: 14 Jul 2025, 2:34 p.m. | Last Modified: 14 Jul 2025, 3 p.m.

Panel Version: 4.26

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Ciliary dyskinesia, primary, 37, OMIM:617577; ciliary dyskinesia, primary, 37, MONDO:0033204

Publications

• 25927852
• 31765523
• 34210339

I don't know

Initial gene list and info collated by Ian Berry Leeds Genetics Laboratory November 2018 on behalf of the GMS Respiratory specialist test group. Gene Symbol submitted: DNAH1; Suggested initial gene rating: Amber; Evidence for inclusion: Only one case of PCD.; Evidence for exclusion: Most homozygote knockouts have spermatogenic failure, no other PCD symptoms. PCD association based on single pair of sisters with unvalidated missense.; Technical notes (e.g. non-coding/CNV mutations requiring coverage?): none given

Created: 5 Dec 2018, 1:54 p.m.

Red List (low evidence)

Associated with phenotype in OMIM, not in G2P. At least one variant reported in 2 consanguineous Saudi Arabian sisters that segregated with the disease in this family and was not found in controls

Created: 21 Aug 2017, 10:59 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
?Ciliary dyskinesia, primary, 37 617577

Publications

• 25927852

Red List (low evidence)

No UK mutations found. So far only connected in one publication of one family with missense mutations (PMID:25927852)

Created: 8 Dec 2015, 4:25 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Too new - not yet linked to the PCD mutations publication

Mode of pathogenicity
Other - please provide details in the comments