Regular Article
Prevalence of AIPL1 Mutations in Inherited Retinal Degenerative Disease

https://doi.org/10.1006/mgme.2000.3001Get rights and content

Abstract

Leber congenital amaurosis (LCA) is the most severe form of inherited retinal dystrophy and the most frequent cause of inherited blindness in children. LCA is usually inherited in an autosomal recessive fashion, although rare dominant cases have been reported. One form of LCA, LCA4, maps to chromosome 17p13 and is genetically distinct from other forms of LCA. We recently identified the gene associated with LCA4, AIPL1 (aryl-hydrocarbon interacting protein-like 1) and identified three mutations that were the cause of blindness in five families with LCA. In this study, AIPL1 was screened for mutations in 512 unrelated probands with a range of retinal degenerative diseases to determine if AIPL1 mutations cause other forms of inherited retinal degeneration and to determine the relative contribution of AIPL1 mutations to inherited retinal disorders in populations worldwide. We identified 11 LCA families whose retinal disorder is caused by homozygous or compound heterozygous AIPL1 mutations. We also identified affected individuals in two apparently dominant families, diagnosed with juvenile retinitis pigmentosa or dominant cone-rod dystrophy, respectively, who are heterozygous for a 12-bp AIPL1 deletion. Our results suggest that AIPL1 mutations cause approximately 7% of LCA worldwide and may cause dominant retinopathy.

References (19)

There are more references available in the full text version of this article.

Cited by (137)

  • Zebrafish and inherited photoreceptor disease: Models and insights

    2022, Progress in Retinal and Eye Research
    Citation Excerpt :

    Arylhydrocarbon receptor interacting-like protein 1 (AIPL1) is a co-chaperone for PDE6 and therefore plays an important role in photoreceptor function (Gopalakrishna et al., 2016). Mutations in AIPL1 cause LCA, CORD, adRP, and arRP (Booij et al., 2005; M. M. Sohocki et al., 2000a, 2000b). Zebrafish aipl1b mutants had abnormal OS disc stacking, green, red, and UV cone opsin mislocalisation, and photoreceptor degeneration at 7 dpf (Iribarne et al., 2017).

  • Aryl hydrocarbon receptor-interacting protein-like 1 is an obligate chaperone of phosphodiesterase 6 and is assisted by the γ-subunit of its client

    2016, Journal of Biological Chemistry
    Citation Excerpt :

    Thus, the unique role of AIPL1FKBP appears to involve its interaction with the prenylated C terminus of PDE6. Most of the missense mutations in AIPL1 linked to LCA lie in the FKBP and TPR domains (Fig. 1) (11, 23, 33–36). We have examined a panel of the FKBP mutants (R38C, K53W (R53W in human AIPL1), V71F, W72S, C89R, V96I, T114I, and Y134F) and TPR mutants (C239R and G262S) for their ability to chaperone PDE6C, both in the absence and in the presence of Pγ.

  • Functional compartmentalization of photoreceptor neurons

    2021, Pflugers Archiv European Journal of Physiology
View all citing articles on Scopus
View full text