Retinal disorders

Gene: NPHP3

Green List (high evidence)

Comment on list classification: Two recent papers showing recessive mutations cause non-syndromic RP.

Created: 7 Jun 2016, 12:10 p.m.

This gene is on the Manchester Genetic Retinal Degeneration Conditions panel (covers known genes for isolated progessive retinal degeneration, Leber congenital amaurosis, macular dystrophy, achromatopsia, congenital stationary night blindness as well as the two most common causes of syndromic blindess Usher and Bardet-Biedl syndromes and additional syndromes including Joubert, Senior-Loken, and Cohen syndrome.

Created: 2 Jun 2016, 8:06 a.m.

I don't know

Publication by Omran et al 2002 linking NPHP3 to Senior-Loken syndrome which involves RP or LCA.
Reports in HGMD are predominantly in patients with nephronophtisis and we have not identified NPHP3 mutations in a disease-causing state in-house. Therefore unclear how relevant this gene is to this panel.

Created: 1 Jun 2016, 10:13 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Meckel syndrome; Senior-Loken syndrome; nephronophthisis

Publications

• Publications in OMIM
• homozygous and compound heterozygous mutations in patients with Meckel syndrome. Multiple publications on HGMD of both missense and loss of function mutations in patients with nephronophthisis. Paper by Olbrich et al 2003 Mutations in a novel gene, NPHP3, cause adolescent nephronophthisis, tapeto-retinal degeneration and hepatic fibrosis.Nat Genet. 2003 Aug
• 34(4):455-9. Omran et al (2002) Identification of a gene locus for Senior-Loken syndrome in the region of the nephronophthisis type 3 gene.J. Am. Soc. Nephrol. 13: 75-79
• NPHP3 mutations have been linked to Senior-Loken syndrome, which involves cystic kidney disease (nephronophthisis) and retinitis pigmentosa or Leber congenital amaurosis.

Variants in this GENE are reported as part of current diagnostic practice