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Cold Spring Harb Mol Case Stud 2017 Jul 01;34:. doi: 10.1101/mcs.a001321.
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Compound heterozygous alterations in intraflagellar transport protein CLUAP1 in a child with a novel Joubert and oral-facial-digital overlap syndrome.

Johnston JJ , Lee C , Wentzensen IM , Parisi MA , Crenshaw MM , Sapp JC , Gross JM , Wallingford JB , Biesecker LG .

Disruption of normal ciliary function results in a range of diseases collectively referred to as ciliopathies. Here we report a child with a phenotype that overlapped with Joubert, oral-facial-digital, and Pallister-Hall syndromes including brain, limb, and craniofacial anomalies. We performed exome-sequence analysis on a proband and both parents, filtered for putative causative variants, and Sanger-verified variants of interest. Identified variants in CLUAP1 were functionally analyzed in a Xenopus system to determine their effect on ciliary function. Two variants in CLUAP1 were identified through exome-sequence analysis, Chr16:g.3558407T>G, c.338T>G, p.(Met113Arg) and Chr16:g.3570011C>T, c.688C>T, p.(Arg230Ter). These variants were rare in the Exome Aggregation Consortium (ExAC) data set of 65,000 individuals (one and two occurrences, respectively). Transfection of mutant CLUAP1 constructs into Xenopus embryos showed reduced protein levels p.(Arg230Ter) and reduced intraflagellar transport p.(Met113Arg). The genetic data show that these variants are present in an affected child, are rare in the population, and result in reduced, but not absent, intraflagellar transport. We conclude that biallelic mutations in CLUAP1 resulted in this novel ciliopathy syndrome in the proband.

PubMed ID: 28679688
PMC ID: PMC5495032
Article link: Cold Spring Harb Mol Case Stud
Grant support: [+]

Species referenced: Xenopus
Genes referenced: cetn4 cluap1 notch1

Disease Ontology terms: syndactyly [+]

Article Images: [+] show captions
References [+] :
Adam, Joubert Syndrome 1993, Pubmed