Limits...
Biallelic mutation of protocadherin-21 (PCDH21) causes retinal degeneration in humans.

Henderson RH, Li Z, Abd El Aziz MM, Mackay DS, Eljinini MA, Zeidan M, Moore AT, Bhattacharya SS, Webster AR - Mol. Vis. (2010)

Bottom Line: 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.Biallelic mutations in the photoreceptor-specific gene PCDH21 cause recessive retinal degeneration in humans.

View Article: PubMed Central - PubMed

Affiliation: Moorfields Eye Hospital, London, UK.

ABSTRACT

Purpose: 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.

Show MeSH

Related in: MedlinePlus

Co-segregation study of members of family 1 using the HaeIII restriction enzyme. Lane 1 is an undigested PCR product (286 bp). Lane 2 is a completely digested PCR product representing the wild-type allele (two products 197 and 56 bp). Affected individuals (lanes 4, 8, 9, and 10) show the homozygous mutant allele (one product 253 bp). Unaffected individuals, carriers (lanes 3, 5, 6, and 7) display the mutant allele in a heterozygous state (two products 253 and 197 bp). M represents the ϕX174RF DNA HaeIII marker.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2806159&req=5

f3: Co-segregation study of members of family 1 using the HaeIII restriction enzyme. Lane 1 is an undigested PCR product (286 bp). Lane 2 is a completely digested PCR product representing the wild-type allele (two products 197 and 56 bp). Affected individuals (lanes 4, 8, 9, and 10) show the homozygous mutant allele (one product 253 bp). Unaffected individuals, carriers (lanes 3, 5, 6, and 7) display the mutant allele in a heterozygous state (two products 253 and 197 bp). M represents the ϕX174RF DNA HaeIII marker.

Mentions: Direct sequencing of the coding regions and intron–exon boundaries of LRRC21 and RGR showed no variants in affected individuals. Sequencing of the 17 coding exons of PCDH21 showed a homozygous single base deletion within exon 4, c.338delG p.G113AfsX1 (Figure 2A). The mutation segregated as a recessive allele in the family (Figure 3) and was not detected in 292 control chromosomes (86 UK blood donors, European Collection of Cell Cultures (ECACC) and 60 ethnically matched control individuals). In addition, the specific change was not found in a panel of DNA from 192 arRP and 96 Leber congenital amaurosis (LCA) patients recruited from Moorfields Eye Hospital (London, UK).


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

Henderson RH, Li Z, Abd El Aziz MM, Mackay DS, Eljinini MA, Zeidan M, Moore AT, Bhattacharya SS, Webster AR - Mol. Vis. (2010)

Co-segregation study of members of family 1 using the HaeIII restriction enzyme. Lane 1 is an undigested PCR product (286 bp). Lane 2 is a completely digested PCR product representing the wild-type allele (two products 197 and 56 bp). Affected individuals (lanes 4, 8, 9, and 10) show the homozygous mutant allele (one product 253 bp). Unaffected individuals, carriers (lanes 3, 5, 6, and 7) display the mutant allele in a heterozygous state (two products 253 and 197 bp). M represents the ϕX174RF DNA HaeIII marker.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2806159&req=5

f3: Co-segregation study of members of family 1 using the HaeIII restriction enzyme. Lane 1 is an undigested PCR product (286 bp). Lane 2 is a completely digested PCR product representing the wild-type allele (two products 197 and 56 bp). Affected individuals (lanes 4, 8, 9, and 10) show the homozygous mutant allele (one product 253 bp). Unaffected individuals, carriers (lanes 3, 5, 6, and 7) display the mutant allele in a heterozygous state (two products 253 and 197 bp). M represents the ϕX174RF DNA HaeIII marker.
Mentions: Direct sequencing of the coding regions and intron–exon boundaries of LRRC21 and RGR showed no variants in affected individuals. Sequencing of the 17 coding exons of PCDH21 showed a homozygous single base deletion within exon 4, c.338delG p.G113AfsX1 (Figure 2A). The mutation segregated as a recessive allele in the family (Figure 3) and was not detected in 292 control chromosomes (86 UK blood donors, European Collection of Cell Cultures (ECACC) and 60 ethnically matched control individuals). In addition, the specific change was not found in a panel of DNA from 192 arRP and 96 Leber congenital amaurosis (LCA) patients recruited from Moorfields Eye Hospital (London, UK).

Bottom Line: 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.Biallelic mutations in the photoreceptor-specific gene PCDH21 cause recessive retinal degeneration in humans.

View Article: PubMed Central - PubMed

Affiliation: Moorfields Eye Hospital, London, UK.

ABSTRACT

Purpose: 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.

Show MeSH
Related in: MedlinePlus