Exome sequencing identifies mutations in CCDC114 as a cause of primary ciliary dyskinesia

Michael R. Knowles, Margaret W. Leigh, Lawrence E. Ostrowski, Lu Huang, Johnny L. Carson, Milan J. Hazucha, Weining Yin, Jonathan S. Berg, Stephanie D. Davis, Sharon D. Dell, Thomas W. Ferkol, Margaret Rosenfeld, Scott D. Sagel, Carlos E. Milla, Kenneth N. Olivier, Emily H. Turner, Alexandra P. Lewis, Michael J. Bamshad, Deborah A. Nickerson, Jay ShendureMaimoona A. Zariwala

Research output: Contribution to journalArticlepeer-review

75 Scopus citations

Abstract

Primary ciliary dyskinesia (PCD) is a genetically heterogeneous, autosomal-recessive disorder, characterized by oto-sino-pulmonary disease and situs abnormalities. PCD-causing mutations have been identified in 14 genes, but they collectively account for only ∼60% of all PCD. To identify mutations that cause PCD, we performed exome sequencing on six unrelated probands with ciliary outer dynein arm (ODA) defects. Mutations in CCDC114, an ortholog of the Chlamydomonas reinhardtii motility gene DCC2, were identified in a family with two affected siblings. Sanger sequencing of 67 additional individuals with PCD with ODA defects from 58 families revealed CCDC114 mutations in 4 individuals in 3 families. All 6 individuals with CCDC114 mutations had characteristic oto-sino-pulmonary disease, but none had situs abnormalities. In the remaining 5 individuals with PCD who underwent exome sequencing, we identified mutations in two genes (DNAI2, DNAH5) known to cause PCD, including an Ashkenazi Jewish founder mutation in DNAI2. These results revealed that mutations in CCDC114 are a cause of ciliary dysmotility and PCD and further demonstrate the utility of exome sequencing to identify genetic causes in heterogeneous recessive disorders.

Original languageEnglish
Pages (from-to)99-106
Number of pages8
JournalAmerican journal of human genetics
Volume92
Issue number1
DOIs
StatePublished - Jan 10 2013

Fingerprint Dive into the research topics of 'Exome sequencing identifies mutations in CCDC114 as a cause of primary ciliary dyskinesia'. Together they form a unique fingerprint.

Cite this