Germline Mutations in an Intermediate Chain Dynein Cause Primary Ciliary Dyskinesia
- 1 November 2001
- journal article
- Published by American Thoracic Society in American Journal of Respiratory Cell and Molecular Biology
- Vol. 25 (5) , 577-583
- https://doi.org/10.1165/ajrcmb.25.5.4619
Abstract
Primary ciliary dyskinesia (PCD) is a genetically heterogeneous, autosomal recessive disorder caused by abnormal ciliary ultrastructure and function, characterized clinically by oto-sino-pulmonary disease. Mutations in an intermediate chain dynein (DNAI1; IC78) have recently been described in PCD patients, with outer dynein arm (ODA) defects. The aims of the current study were to test for novel DNAI1 mutations in 13 PCD patients with ODA defects (from 7 unrelated families) and to assess genotype/phenotype correlations in patients and family members. A previously reported mutation (219+3insT) was detected in three PCD patients from two families. The opposite allele had the novel missense mutation G1874C (W568S) in both affected individuals from one family, and a nonsense mutation G1875A (W568X) in an affected individual from another family. The tryptophan at position 568 is a highly conserved residue in the WD-repeat region, and a mutation is predicted to lead to abnormal folding of the protein and loss of function. None of these mutations were found in 32 other PCD patients with miscellaneous ciliary defects. Mutations in DNAI1 are causative for PCD with ODA defects, and are likely the genetic origin of clinical disease in some PCD patients with ultrastructural defects in the ODA.Keywords
This publication has 24 references indexed in Scilit:
- Loss-of-Function Mutations in a Human Gene Related to Chlamydomonas reinhardtii Dynein IC78 Result in Primary Ciliary DyskinesiaAmerican Journal of Human Genetics, 1999
- Primary ciliary dyskinesia: diagnosis and standards of careEuropean Respiratory Journal, 1998
- The 78,000-M(r) intermediate chain of Chlamydomonas outer arm dynein is a microtubule-binding protein.The Journal of cell biology, 1995
- Canine hereditary ceroid‐lipofuscinosis: Evidence for a defect in the carnitine biosynthetic pathwayAmerican Journal of Medical Genetics, 1995
- Primarily nasal origin of exhaled nitric oxide and absence in Kartagener's syndromeEuropean Respiratory Journal, 1994
- Fertility in men with primary ciliary dyskinesia presenting with respiratory infection.Thorax, 1994
- Identification of oda6 as a Chlamydomonas dynein mutant by rescue with the wild-type gene.The Journal of cell biology, 1991
- Protein‐protein interactions in the 18S ATPase of Chlamydomonas outer dynein armsCell Motility, 1986
- The Immotile-Cilia SyndromeNew England Journal of Medicine, 1977
- A Human Syndrome Caused by Immotile CiliaScience, 1976