title: Nonsense mutation in coiled-coil domain containing 151 gene (CCDC151) causes primary ciliary dyskinesia.
abstract: Primary ciliary dyskinesia (PCD) is an autosomal-recessive disorder characterized by impaired ciliary function that leads to subsequent clinical phenotypes such as chronic sinopulmonary disease. PCD is also a genetically heterogeneous disorder with many single gene mutations leading to similar clinical phenotypes. Here, we present a novel PCD causal gene, coiled-coil domain containing 151 (CCDC151), which has been shown to be essential in motile cilia of many animals and other vertebrates but its effects in humans was not observed until currently. We observed a novel nonsense mutation in a homozygous state in the CCDC151 gene (NM_145045.4:c.925G>T:p.[E309*]) in a clinically diagnosed PCD patient from a consanguineous family of Arabic ancestry. The variant was absent in 238 randomly selected individuals indicating that the variant is rare and likely not to be a founder mutation. Our finding also shows that given prior knowledge from model organisms, even a single whole-exome sequence can be sufficient to discover a novel causal gene.
authors.affiliation: College of Medicine, King Saud University, Riyadh, 11533, Kingdom of Saudi Arabia.
authors.forename: Muslim M
authors.initials: MM
authors.lastname: Alsaadi
authors.forename: A Mesut
authors.initials: AM
authors.lastname: Erzurumluoglu
authors.forename: Santiago
authors.initials: S
authors.lastname: Rodriguez
authors.forename: Philip A I
authors.initials: PA
authors.lastname: Guthrie
authors.forename: Tom R
authors.initials: TR
authors.lastname: Gaunt
authors.forename: Hager Z
authors.initials: HZ
authors.lastname: Omar
authors.forename: Mohammad
authors.initials: M
authors.lastname: Mubarak
authors.forename: Khalid K
authors.initials: KK
authors.lastname: Alharbi
authors.forename: Ammar C
authors.initials: AC
authors.lastname: Al-Rikabi
authors.forename: Ian N M
authors.initials: IN
authors.lastname: Day
mesh_terms: D002352:Carrier Proteins / Q000235:genetics*; D018389:Codon, Nonsense; D020022:Genetic Predisposition to Disease; D006801:Humans; D007619:Kartagener Syndrome / Q000235:genetics*
chemical_list: D002352:Carrier Proteins; D018389:Codon, Nonsense; C000599248:ODAD3 protein, human
keywords: CCDC151; ciliopathy; primary ciliary dyskinesia; respiratory cilia