Journal
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
Volume 174, Issue 8, Pages 858-866Publisher
AMER THORACIC SOC
DOI: 10.1164/rccm.200603-370OC
Keywords
cilia; dynein; dextrocardia; Kartagener syndrome; mutation
Categories
Funding
- NCRR NIH HHS [M01 RR00046-42, 5 U54 RR019480] Funding Source: Medline
- NHLBI NIH HHS [1 R01 HL071798] Funding Source: Medline
- Wellcome Trust Funding Source: Medline
Ask authors/readers for more resources
Rationale: Primary ciliary dyskinesia (PCD) is a rare, usually autosomal recessive, genetic disorder characterized by ciliary dysfunction, sino-pulmonary disease, and situs inversus. Disease-causing mutations have been reported in DNAI1 and DNAH5 encoding outer dynein arm (ODA) proteins of cilia. Objectives:We analyzed DNAI1 to identify disease-causing mutations in PCD and to determine if the previously reported IVS1 + 2_3insT (219+3insT) mutation represents a founder or hot spot mutation. Methods: Patients with PCD from 179 unrelated families were studied. Exclusion mapping showed no linkage to DNAI1 for 13 families,the entire coding region was sequenced in a patient from the remaining 166 families. Reverse transcriptase-polymerase chain reaction (RT-PCR) was performed on nasal epithelial RNA in 14 families. Results: Mutations in DNAI1 including 12 novel mutations were identified in 16 of 179 (9%) families; 14 harbored biallelic mutations. Deep intronic splice mutations were not identified by reverse transcriptase-polymerase chain reaction. The prevalence of mutations in families with defined ODA defect was 13%; no mutations were found in patients without a defined ODA defect. The previously reported IVS1 +2_3insT mutation accounted for 57% (17/30) of mutant alleles, and marker analysis indicates a common founder for this mutation. Seven mutations occurred in three exons (13, 16, and 17); taken together with previous reports, these three exons are emerging as mutation clusters harboring 29% (12/42) of mutant alleles. Conclusions: A total of 10% of patients with PCD are estimated to harbor mutations in DNA11; most occur as a common founder IVS1 +2_3insT or in exons 13, 16, and 17. This information is useful for establishing a clinical molecular genetic test for PCD.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available