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Publication year
2010Author(s)
Source
Nature Genetics, 42, 10, (2010), pp. 840-50ISSN
Annotation
01 oktober 2010
Publication type
Article / Letter to editor
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Organization
Human Genetics
Ophthalmology
Journal title
Nature Genetics
Volume
vol. 42
Issue
iss. 10
Page start
p. 840
Page end
p. 50
Subject
IGMD 3: Genomic disorders and inherited multi-system disorders; IGMD 9: Renal disorder; NCMLS 6: Genetics and epigenetic pathways of diseaseAbstract
Nephronophthisis-related ciliopathies (NPHP-RC) are recessive disorders that feature dysplasia or degeneration occurring preferentially in the kidney, retina and cerebellum. Here we combined homozygosity mapping with candidate gene analysis by performing 'ciliopathy candidate exome capture' followed by massively parallel sequencing. We identified 12 different truncating mutations of SDCCAG8 (serologically defined colon cancer antigen 8, also known as CCCAP) in 10 families affected by NPHP-RC. We show that SDCCAG8 is localized at both centrioles and interacts directly with OFD1 (oral-facial-digital syndrome 1), which is associated with NPHP-RC. Depletion of sdccag8 causes kidney cysts and a body axis defect in zebrafish and induces cell polarity defects in three-dimensional renal cell cultures. This work identifies loss of SDCCAG8 function as a cause of a retinal-renal ciliopathy and validates exome capture analysis for broadly heterogeneous single-gene disorders.
This item appears in the following Collection(s)
- Academic publications [238441]
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- Faculty of Medical Sciences [90373]
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