ClinGen Dosage Sensitivity Curation Page


  • Curation Status: Complete

Location Information

Select assembly: (NC_000012.11) (NC_000012.12)
  • Haploinsufficiency score: Gene associated with autosomal recessive phenotype
  • Strength of Evidence (disclaimer): Gene associated with autosomal recessive phenotype

Haploinsufficiency phenotype comments:

Changes in CEP290 have been associated with several different phenotypes, including Joubert syndrome type 5, Senior-Loken syndrome type 6, Leber congenital amaurosis type 10, Meckel syndrome type 4, Bardet-Biedl syndrome type 14, etc. These conditions are generally thought of as being inherited in an autosomal recessive manner. In a mutation overview by Coppieters et al. (2010), the authors state that "although these are essentially autosomal recessive (AR) monogenic diseases, epistatic effects of modifier alleles in additional ciliary genes should not be underestimated in the development of their phenotypes" (PMID: 20690115). The authors also note that for 18 patients previously reported in the literature, only one mutation was identified. They postulate that this might be due to an inability of standard PCR-based techniques to identify mutations such as deep intronic variants, large genomic rearrangements or regulatory mutations located in promoter or enhancer/silencer elements; the idea that heterozygous CEP290 mutation might represent a modifying allele, potentially influencing the clinical expression of two AR mutations in another ciliary gene; and the possibility that another as yet unidentified NPHP gene could segregate in linkage disequilibrium with CEP290 in these families. See also PMID: 19764032.

  • Triplosensitivity score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity