Loss of the Metalloprotease ADAM9 Leads to Cone-Rod Dystrophy in Humans and Retinal Degeneration in Mice

David A. Parry, Carmel Toomes, Lina Bida, Michael Danciger, Katherine V. Towns, Martin McKibbin, Samuel G. Jacobson, Clare V. Logan, Manir Ali, Jacquelyn Bond, Rebecca Chance, Steven Swendeman, Lauren L. Daniele, Kelly Springell, Matthew Adams, Colin A. Johnson, Adam P. Booth, Hussain Jafri, Yasmin Rashid, Eyal BaninTim M. Strom, Debora B. Farber, Dror Sharon, Carl P. Blobel, Edward N Pugh Jr, Eric A. Pierce, Chris F. Inglehearn

Research output: Contribution to journalArticlepeer-review

59 Scopus citations


Cone-rod dystrophy (CRD) is an inherited progressive retinal dystrophy affecting the function of cone and rod photoreceptors. By autozygosity mapping, we identified null mutations in the ADAM metallopeptidase domain 9 (ADAM9) gene in four consanguineous families with recessively inherited early-onset CRD. We also found reduced photoreceptor responses in Adam9 knockout mice, previously reported to be asymptomatic. In 12-month-old knockout mice, photoreceptors appear normal, but the apical processes of the retinal pigment epithelium (RPE) cells are disorganized and contact between photoreceptor outer segments (POSs) and the RPE apical surface is compromised. In 20-month-old mice, there is clear evidence of progressive retinal degeneration with disorganized POS and thinning of the outer nuclear layer (ONL) in addition to the anomaly at the POS-RPE junction. RPE basal deposits and macrophages were also apparent in older mice. These findings therefore not only identify ADAM9 as a CRD gene but also identify a form of pathology wherein retinal disease first manifests at the POS-RPE junction.

Original languageEnglish (US)
Pages (from-to)683-691
Number of pages9
JournalAmerican Journal of Human Genetics
Issue number5
StatePublished - May 15 2009
Externally publishedYes

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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