Biallelic mutation of Protocadherin-21 (PCDH21) causes retinal degeneration in humans

[摘要] Purpose: To describe the clinicalfindings and mutations in affected members of two families with anautosomal recessive retinal dystrophy associated with mutations in theprotocadherin-21 (PCDH21) gene. Methods: A full genome scan of membersof two consanguineous families segregating an autosomal recessiveretinal dystrophy was performed and regions identicalby descent identified. Positional candidate genes were identified andsequenced. All patients had a detailed ophthalmic examination,including electroretinography and retinal imaging. Results: Affected members of bothfamilies showed identical homozygosity for an overlapping region ofchromosome 10q. Sequencing of a candidate gene, PCDH21, showedtwo separate homozygous single-base deletions, c.337delG (p.G113AfsX1)and c.1459delG (p.G487GfsX20), which were not detected in 282 controlchromosomes. Affected members of the two families first reportednyctalopia in late teenage years and retained good central vision untiltheir late 30s. No color vision was detected in any proband. The fundusappearance included the later development of characteristic circularpatches of pigment epithelial atrophy at the macula and in theperipheral retina. Conclusions: Biallelic mutations in thephotoreceptor-specific gene PCDH21 cause recessive retinaldegeneration in humans.

[学科分类] 生物化学/生物物理