Chris Inglehearn
Understanding the causes of eye diseases
Our work aims to determine the causes of human visual defects and to find out more about normal eye function. Ultimately we aim to contribute to the search for cures for blinding diseases.
We carried out an empirical investigation of the theoretical basis of autozygosity (homozygosity) mapping (Woods et al. 2006) and used it to identify the LCA5 gene, defective in Leber congenital amaurosis. Leber amaurosis is the commonest form of congenital blindness and is an autosomal recessive disorder that displays considerable locus heterogeneity. With colleagues from the Netherlands we identified lebercilin, a ciliary and microtubule-associated protein whose gene is mutated in LCA5 mapping to chromsome 6q.
In addition we played a major role in an international collaboration which identified SLC4A11 as the defective gene in corneal hereditary endothelial dystrophy (Vithana et al. 2006).
Recently, we have identified CNNM4 as the gene for Jalili syndrome (cone-rod dystrophy and dentinogenesis imperfecta).
We also continue our ongoing interest in determining the cellular basis for splicing factor retinitis pigmentosa. Finally, we translate research findings into a clinical setting by piloting diagnostic services for inherited retinal diseases, in collaboration with clinical colleagues.
Recent publications:
Parry DA, Mighell AJ, El-Sayed W, Shore RC, Jalili IK, Dollfus H, Bloch-Zupan A, Carlos R, Carr IM, Downey LM, Blain KM, Mansfield DC, Shahrabi M, Heidari M, Aref P, Abbasi M, Michaelides M, Moore AT, Kirkham J, Inglehearn CF (2009). Mutations in CNNM4 cause Jalili syndrome, consisting of autosomal-recessive cone-rod dystrophy and amelogenesis imperfecta. Am J Hum Genet 84:266-73.
Den Hollander A, Koenekoop R, Mohamed M, Arts H, Boldt K, Towns K, Sedmark T, Beer M, Nagel-Wolfrum K, McKibbin M, Dharmaraj S, Lopez I, Ivings L, Williams G, Springell K, Woods CG, Jafri H, Rashid Y, Strom T, Zwaag B, Gosens I, Kersten F, Veltman J, Van Wijk E, Zonneveld M, Beersum S, Maumenee I, Wolfrum U, Cheetham M, Ueffing M, Cremers F, Inglehearn CF, Roepman R (2007). Mutations in lebercilin, a novel ciliary protein, cause Leber congenital amaurosis. Nature Genet 39:889-95
Vithana E, Morgan P, Sundaresan P, Ebenezer N, Tan DT, Mohamed MD, Anand S, Khine KO, Venkataraman D, Yong V, Salto-Tellez M, Venkataraman A, Guo K, Hemadevi B, Srinivasan M, Prajna V, Khine M, Casey JR, Inglehearn CF, Aung T (2006). Mutations in sodium-borate cotransporter SLC4A11 cause recessive congenital hereditary endothelial dystrophy (CHED2). Nature Genet 38:755-7
Woods CG, Springell K, Hampshire D, Mohamed M, McKibbin M, Cox J, Stern R, Raymond F, Malik S, Karbani G, Ahmed M, Bond J, Clayton D, Inglehearn CF (2006). Quantification of homozygosity in consanguineous individuals with autosomal recessive disease. Am J Hum Genet 78:889-96
Leber congenital amaurosis is the commonest form of congenital blindness. One gene, LCA5 on Chr. 6q14, encodes the ciliary protein lebercilin. The image shows lebercilin co-localized with tubulin in cultured cells.