德国雷根斯堡大学近日发表公报说，其研究者与美国同行发现了导致色素性视网膜炎等遗传性眼部疾病的基因性病因。该成果有助于改善遗传性眼部疾病的治疗方法。
人类视网膜的感光细胞可分为视杆细胞和视锥细胞，它们能接受外界光线刺激并产生电脉冲到达大脑，最终形成视觉。视杆细胞和视锥细胞的损坏是典型遗传性眼部疾病，如果病情严重可造成失明。
德国与美国研究人员应用染色质免疫沉淀测序的方法，在老鼠的视网膜上进行实验，发现名为视网膜锥杆体同源盒（CRX）的基因，与所有视杆细胞和视锥细胞的基因改变有关。利用这一方法，研究小组证实受视网膜锥杆体同源盒基因影响的FAM161A基因突变，是造成遗传性眼部疾病色素性视网膜炎的原因。
研究人员表示，他们将进一步研究FAM161A基因的其他特性，以及找到受视网膜锥杆体同源盒基因影响的更多致病基因。
生物谷推荐原文出处：
The American Journal of Human Genetics doi:10.1016/j.ajhg.2010.07.018
Nonsense Mutations in FAM161A Cause RP28-Associated Recessive Retinitis Pigmentosa
Thomas Langmann1, 9, Silvio Alessandro Di Gioia2, 9, Isabella Rau3, 9, Heidi St?hr1, Nela S. Maksimovic3, 11, Joseph C. Corbo4, Agnes B. Renner5, Eberhart Zrenner6, Govindasamy Kumaramanickavel7, Marcus Karlstetter1, Yvan Arsenijevic8, Bernhard H.F. Weber1, Andreas Gal3, 10, , and Carlo Rivolta2, 10, ,
1 Institute of Human Genetics, University of Regensburg, D-93053 Regensburg, Germany
2 Department of Medical Genetics, University of Lausanne, CH-1005 Lausanne, Switzerland
3 Institute of Human Genetics, University Medical Centre Hamburg-Eppendorf, D-20246 Hamburg, Germany
4 Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA
5 Department of Ophthalmology, University Medical Center Regensburg, D-93053 Regensburg, Germany
6 Centre for Ophthalmology, Institute for Ophthalmic Research, University of Tübingen, D-72076 Tübingen, Germany
7 Department of Genetics and Molecular Biology, Sankara Nethralaya, Chennai - 600 006, India
8 Unit of Gene Therapy and Stem Cell Biology, Jules-Gonin Eye Hospital, University of Lausanne, CH-1004 Lausanne, Switzerland
Retinitis pigmentosa (RP) is a degenerative disease of the retina leading to progressive loss of vision and, in many instances, to legal blindness at the end stage. The RP28 locus was assigned in 1999 to the short arm of chromosome 2 by homozygosity mapping in a large Indian family segregating autosomal-recessive RP (arRP). Following a combined approach of chromatin immunoprecipitation and parallel sequencing of genomic DNA, we identified a gene, FAM161A, which was shown to carry a homozygous nonsense mutation (p.Arg229X) in patients from the original RP28 pedigree. Another homozygous FAM161A stop mutation (p.Arg437X) was detected in three subjects from a cohort of 118 apparently unrelated German RP patients. Age at disease onset in these patients was in the second to third decade, with severe visual handicap in the fifth decade and legal blindness in the sixth to seventh decades. FAM161A is a phylogenetically conserved gene, expressed in the retina at relatively high levels and encoding a putative 76 kDa protein of unknown function. In the mouse retina, Fam161a mRNA is developmentally regulated and controlled by the transcription factor Crx, as demonstrated by chromatin immunoprecipitation and organotypic reporter assays on explanted retinas. Fam161a protein localizes to photoreceptor cells during development, and in adult animals it is present in the inner segment as well as the outer plexiform layer of the retina, the synaptic interface between photoreceptors and their efferent neurons. Taken together, our data indicate that null mutations in FAM161A are responsible for the RP28-associated arRP.
