Date Posted: 04 March 2010
An international research consortium led by a team at the University of California, San Diego have shown that mutations in AHI1 (Abelson helper integration site-1 gene) are associated with abnormal photoreceptor structure and an abnormal distribution of opsin in the photoreceptor cell layer. AHI1 is known to code for a cilium localised gene which, when mutated, can give rise to Joubert syndrome, a rare genetic disorder affecting balance and co-ordination. The finding underscores the biological significance of cilia in the healthy functioning of cells and tissues of the retina, cerebellum and kidney.
Ciliopathies (diseases involving dysfunction of the cilia) are gaining recognition as a distinct class of pathologies within a broad spectrum of poorly understood disorders. Mutations in the AHI1 gene are identified in approximately 12% of individuals with Joubert syndrome and in 20% of individuals diagnosed with both Joubert syndrome and LCA (Leber's congenital amaurosis). Genetic analysis of Ahi1-null mice by the research team demonstrated dosage sensitive interaction with another ciliopathy related gene, Nphp1 (nephrocystin-1). The research consortium have been able to show that mutations in an allele of AHI1 are associated with a more than sevenfold increase in relative risk of retinal degeneration within individuals suffering the hereditary kidney disease, nephronophthisis.
The authors of the study suggest that their "example within the ciliopathies shows that mutational analysis of other causative genes from the broader clinical spectrum can yield substantial insight into the genetics and pathogenesis of hetero-geneous syndromic disorders". Analysis of photoreceptor cells within the retina of mouse models suggested that apoptotic cell death was occurring due to a toxic accumulation of rhodopsin which supported a long held theory that protein mis-trafficking may be a key pathological step between genotype and phenotype in many inherited retinal diseases. Results from the study may lead to improved screening and therapeutic opportunities in the management of congenital blindness. [Louie et al, Nature Genetics, Vol. 42, No. 2 p.175].
no comments posted
Your IP address: 38.107.191.84