Unknown

Dataset Information

0

Mutations in DYNC2LI1 disrupt cilia function and cause short rib polydactyly syndrome.

ABSTRACT: The short rib polydactyly syndromes (SRPSs) are a heterogeneous group of autosomal recessive, perinatal lethal skeletal disorders characterized primarily by short, horizontal ribs, short limbs and polydactyly. Mutations in several genes affecting intraflagellar transport (IFT) cause SRPS but they do not account for all cases. Here we identify an additional SRPS gene and further unravel the functional basis for IFT. We perform whole-exome sequencing and identify mutations in a new disease-producing gene, cytoplasmic dynein-2 light intermediate chain 1, DYNC2LI1, segregating with disease in three families. Using primary fibroblasts, we show that DYNC2LI1 is essential for dynein-2 complex stability and that mutations in DYNC2LI1 result in variable length, including hyperelongated, cilia, Hedgehog pathway impairment and ciliary IFT accumulations. The findings in this study expand our understanding of SRPS locus heterogeneity and demonstrate the importance of DYNC2LI1 in dynein-2 complex stability, cilium function, Hedgehog regulation and skeletogenesis.

SUBMITTER: Taylor SP 

PROVIDER: S-EPMC4470332 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

Json Xml
altmetric image

Publications

Mutations in DYNC2LI1 disrupt cilia function and cause short rib polydactyly syndrome.

Taylor S Paige SP   Dantas Tiago J TJ   Duran Ivan I   Wu Sulin S   Lachman Ralph S RS   Nelson Stanley F SF   Cohn Daniel H DH   Vallee Richard B RB   Krakow Deborah D  

Nature communications 20150616

The short rib polydactyly syndromes (SRPSs) are a heterogeneous group of autosomal recessive, perinatal lethal skeletal disorders characterized primarily by short, horizontal ribs, short limbs and polydactyly. Mutations in several genes affecting intraflagellar transport (IFT) cause SRPS but they do not account for all cases. Here we identify an additional SRPS gene and further unravel the functional basis for IFT. We perform whole-exome sequencing and identify mutations in a new disease-produci  ...[more]

Similar Datasets

Unknown NEK1 mutations cause short-rib polydactyly syndrome type majewski.
| S-EPMC3014367 | biostudies-literature
Unknown IFT52 mutations destabilize anterograde complex assembly, disrupt ciliogenesis and result in short rib polydactyly syndrome.
| S-EPMC5291235 | biostudies-literature
Unknown DYNC2H1 mutations cause asphyxiating thoracic dystrophy and short rib-polydactyly syndrome, type III.
| S-EPMC2681009 | biostudies-literature
Unknown Mutations in KIAA0586 Cause Lethal Ciliopathies Ranging from a Hydrolethalus Phenotype to Short-Rib Polydactyly Syndrome.
| S-EPMC4573270 | biostudies-literature
Unknown WDR34 mutations that cause short-rib polydactyly syndrome type III/severe asphyxiating thoracic dysplasia reveal a role for the NF-?B pathway in cilia.
| S-EPMC3824112 | biostudies-literature
Unknown Destabilization of the IFT-B cilia core complex due to mutations in IFT81 causes a Spectrum of Short-Rib Polydactyly Syndrome.
| S-EPMC5035930 | biostudies-literature
Unknown Human and mouse mutations in WDR35 cause short-rib polydactyly syndromes due to abnormal ciliogenesis.
| S-EPMC3071922 | biostudies-literature
Unknown A Rare Cause of Persistent Pulmonary Hypertension Resistant to Therapy in The Newborn: Short-Rib Polydactyly Syndrome.
| S-EPMC4452873 | biostudies-literature
Unknown Short-rib polydactyly and Jeune syndromes are caused by mutations in WDR60.
| S-EPMC3769922 | biostudies-literature
Unknown Tctex1d2 associates with short-rib polydactyly syndrome proteins and is required for ciliogenesis.
| S-EPMC4614626 | biostudies-literature