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1: Nat Genet. 2008 Jul;40(7):892-6. Epub 2008 May 30.
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Age-related macular degeneration is associated with an unstable ARMS2 (LOC387715) mRNA.

Fritsche LG, Loenhardt T, Janssen A, Fisher SA, Rivera A, Keilhauer CN, Weber BH.

Institute of Human Genetics, University of Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany.

Age-related macular degeneration (AMD) is a prevalent multifactorial disorder of the central retina. Genetic variants at two chromosomal loci, 1q31 and 10q26, confer major disease risks, together accounting for more than 50% of AMD pathology. Signals at 10q26 center over two nearby genes, ARMS2 (age-related maculopathy susceptibility 2, also known as LOC387715) and HTRA1 (high-temperature requirement factor A1), suggesting two equally probable candidates. Here we show that a deletion-insertion polymorphism in ARMS2 (NM_001099667.1:c.(*)372_815del443ins54) is strongly associated with AMD, directly affecting the transcript by removing the polyadenylation signal and inserting a 54-bp element known to mediate rapid mRNA turnover. As a consequence, expression of ARMS2 in homozygous carriers of the indel variant is not detectable. Confirming previous findings, we demonstrate a mitochondrial association of the normal protein and further define its retinal localization to the ellipsoid region of the photoreceptors. Our data suggest that ARMS2 has a key role in AMD, possibly through mitochondria-related pathways.

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PMID: 18511946 [PubMed - indexed for MEDLINE]