Author/Editor		Sergouniotis, Panagiotis I.; Davidson, Alice E.; Mackay, Donna S.; Li, Zheng; Xu, Yang; Plagnol, Vincent; Moore, Anthony T.; Webster, Andrew R.
Title		Recessive mutations in KCNJ13, encoding an inwardly rectifying potassium channel subunit, cause leber congenital amaurosis
Type		članek
Vol. and No.		Letnik 89, št. 1
Publication year		2011
Volume		str. 183-190
ISSN		0002-9297 - American journal of human genetics
Language		eng
Abstract		Inherited retinal degenerations, including retinitis pigmentosa (RP) and Leber congenital amaurosis (LCA), comprise a group of disordersshowing high genetic and allelic heterogeneity. The determination of a full catalog of genes that can, when mutated, cause humanretinal disease is a powerful means to understand the molecular physiology and pathology of the human retina. As more genes arefound, remaining ones are likely to be rarer and/or unexpected candidates. Here, we identify a family in which all known RP/LCA-relatedgenes are unlikely to be associated with their disorder. A combination of homozygosity mapping and exome sequencing identifiesa homozygous nonsense mutation, c.496C>T (p.Arg166X), in a gene,KCNJ13, encoding a potassium channel subunit Kir7.1. A screenof a further 333 unrelated individuals with recessive retinal degeneration identified an additional proband, homozygous for a missensemutation, c.722T>C (p.Leu241Pro), in the same gene. The three affected members of the two families have been diagnosed with LCA. Allhave a distinct and unusual retinal appearance and a similar early onset of visual loss, suggesting both impaired retinal development andprogressive retinal degeneration, involving both rod and cone pathways. Examination of heterozygotes revealed no ocular disease. Thisfinding implicates Kir7.1 as having an important role in human retinal development and maintenance. This disorder adds to a smalldiverse group of diseases consequent upon loss or reduced function of inwardly rectifying potassium channels affecting variousorgans. The distinct retinal phenotype that results from biallelic mutations inKCNJ13should facilitate the molecular diagnosis in furtherfamilies.
Keywords		Leber congenital amaurosis recessive mutations retina Leberjeva bolezen recesivne mutacije mrežnica