Biallelic mutation of protocadherin-21 (PCDH21) causes retinal degeneration in humans.
OBJECTIVE
To describe the clinical findings and mutations in affected members of two families with an autosomal recessive retinal dystrophy associated with mutations in the protocadherin-21 (PCDH21) gene.


METHODS
A full genome scan of members of two consanguineous families segregating an autosomal recessive retinal dystrophy was performed and regions identical by descent identified. Positional candidate genes were identified and sequenced. All patients had a detailed ophthalmic examination, including electroretinography and retinal imaging.


RESULTS
Affected members of both families showed identical homozygosity for an overlapping region of chromosome 10q. Sequencing of a candidate gene, PCDH21, showed two separate homozygous single-base deletions, c.337delG (p.G113AfsX1) and c.1459delG (p.G487GfsX20), which were not detected in 282 control chromosomes. Affected members of the two families first reported nyctalopia in late teenage years and retained good central vision until their late 30s. No color vision was detected in any proband. The fundus appearance included the later development of characteristic circular patches of pigment epithelial atrophy at the macula and in the peripheral retina.


CONCLUSIONS
Biallelic mutations in the photoreceptor-specific gene PCDH21 cause recessive retinal degeneration in humans.
Henderson
Robert H
RH
Moorfields Eye Hospital, London, UK.
Li
Zheng
Z
Abd El Aziz
Mai M
MM
Mackay
Donna S
DS
Eljinini
Mohammad A
MA
Zeidan
Marwan
M
Moore
Anthony T
AT
Bhattacharya
Shomi S
SS
Webster
Andrew R
AR
D000328:Adult; D000483:Alleles; D000595:Amino Acid Sequence; D001483:Base Sequence; D000070585:Cadherin Related Proteins; D015820:Cadherins / Q000737:chemistry / Q000235:genetics*; D020090:Chromosome Segregation / Q000235:genetics; D004252:DNA Mutational Analysis; D004596:Electroretinography; D005091:Exons / Q000235:genetics; D005190:Family; D005260:Female; D005654:Fundus Oculi; D006801:Humans; D008297:Male; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics*; D010375:Pedigree; D017434:Protein Structure, Tertiary; D012162:Retinal Degeneration / Q000235:genetics*
C442481:CDHR1 protein, human; D000070585:Cadherin Related Proteins; D015820:Cadherins; D009419:Nerve Tissue Proteins