Limits...
Mutations in the β-subunit of rod phosphodiesterase identified in consanguineous Pakistani families with autosomal recessive retinitis pigmentosa.

Ali S, Riazuddin SA, Shahzadi A, Nasir IA, Khan SN, Husnain T, Akram J, Sieving PA, Hejtmancik JF, Riazuddin S - Mol. Vis. (2011)

Bottom Line: During exclusion analyses both families localized to chromosome 4p, harboring PDE6β, a gene previously associated with autosomal recessive RP.Bioinformatic analyses suggested that both mutations are deleterious for the native three-dimensional structure of the PDE6β protein.These results strongly suggest that mutations in PDE6β are responsible for the disease phenotype in the consanguineous Pakistani families.

View Article: PubMed Central - PubMed

Affiliation: National Centre of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan.

ABSTRACT

Purpose: This study was designed to identify pathogenic mutations causing autosomal recessive retinitis pigmentosa (RP) in consanguineous Pakistani families.

Methods: Two consanguineous families affected with autosomal recessive RP were identified from the Punjab Province of Pakistan. All affected individuals underwent a thorough ophthalmologic examination. Blood samples were collected, and genomic DNAs were extracted. Exclusion analysis was completed, and two-point LOD scores were calculated. Bidirectional sequencing of the β subunit of phosphodiesterase 6 (PDE6β) was completed.

Results: During exclusion analyses both families localized to chromosome 4p, harboring PDE6β, a gene previously associated with autosomal recessive RP. Sequencing of PDE6β identified missense mutations: c.1655G>A (p.R552Q) and c.1160C>T (p.P387L) in families PKRP161 and PKRP183, respectively. Bioinformatic analyses suggested that both mutations are deleterious for the native three-dimensional structure of the PDE6β protein.

Conclusions: These results strongly suggest that mutations in PDE6β are responsible for the disease phenotype in the consanguineous Pakistani families.

Show MeSH

Related in: MedlinePlus

The sequence chromatograms of families PKRP161 and PKRP183. A: Unaffected individual 20 of PKRP161 heterozygous. B: Affected individual 17 homozygous for a single base change: c.1655G>A, leading to an Arginine to Glutamine substitution: p.R552Q. C: Unaffected individual 11 of family PKRP183 heterozygous. D: Affected individual 7 homozygous for a base change: c.1160 C>T, leading to Proline to Leucine substitution: p.P387L.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3108895&req=5

f4: The sequence chromatograms of families PKRP161 and PKRP183. A: Unaffected individual 20 of PKRP161 heterozygous. B: Affected individual 17 homozygous for a single base change: c.1655G>A, leading to an Arginine to Glutamine substitution: p.R552Q. C: Unaffected individual 11 of family PKRP183 heterozygous. D: Affected individual 7 homozygous for a base change: c.1160 C>T, leading to Proline to Leucine substitution: p.P387L.

Mentions: The linked region on chromosome 4pter-p16.2 harbors PDE6β, a gene that has previously been associated with the causality of arRP. We sequenced all coding exons, exon–intron boundaries, and the 5′ and 3′ untranslated regions of PDE6β. In PKRP161 we identified a missense mutation c.1655G>A (Figure 4), which results in an arginine residue substituted by a glutamine residue at position 552: p.R552Q. Similarly, we identified the novel missense variation c.1160 C>T in PKRP183 (Figure 4), which leads to a proline residue substituted by leucine at position 387: p.P387L. None of these two variations were present in 192 ethnically matched control chromosomes.


Mutations in the β-subunit of rod phosphodiesterase identified in consanguineous Pakistani families with autosomal recessive retinitis pigmentosa.

Ali S, Riazuddin SA, Shahzadi A, Nasir IA, Khan SN, Husnain T, Akram J, Sieving PA, Hejtmancik JF, Riazuddin S - Mol. Vis. (2011)

The sequence chromatograms of families PKRP161 and PKRP183. A: Unaffected individual 20 of PKRP161 heterozygous. B: Affected individual 17 homozygous for a single base change: c.1655G>A, leading to an Arginine to Glutamine substitution: p.R552Q. C: Unaffected individual 11 of family PKRP183 heterozygous. D: Affected individual 7 homozygous for a base change: c.1160 C>T, leading to Proline to Leucine substitution: p.P387L.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3108895&req=5

f4: The sequence chromatograms of families PKRP161 and PKRP183. A: Unaffected individual 20 of PKRP161 heterozygous. B: Affected individual 17 homozygous for a single base change: c.1655G>A, leading to an Arginine to Glutamine substitution: p.R552Q. C: Unaffected individual 11 of family PKRP183 heterozygous. D: Affected individual 7 homozygous for a base change: c.1160 C>T, leading to Proline to Leucine substitution: p.P387L.
Mentions: The linked region on chromosome 4pter-p16.2 harbors PDE6β, a gene that has previously been associated with the causality of arRP. We sequenced all coding exons, exon–intron boundaries, and the 5′ and 3′ untranslated regions of PDE6β. In PKRP161 we identified a missense mutation c.1655G>A (Figure 4), which results in an arginine residue substituted by a glutamine residue at position 552: p.R552Q. Similarly, we identified the novel missense variation c.1160 C>T in PKRP183 (Figure 4), which leads to a proline residue substituted by leucine at position 387: p.P387L. None of these two variations were present in 192 ethnically matched control chromosomes.

Bottom Line: During exclusion analyses both families localized to chromosome 4p, harboring PDE6β, a gene previously associated with autosomal recessive RP.Bioinformatic analyses suggested that both mutations are deleterious for the native three-dimensional structure of the PDE6β protein.These results strongly suggest that mutations in PDE6β are responsible for the disease phenotype in the consanguineous Pakistani families.

View Article: PubMed Central - PubMed

Affiliation: National Centre of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan.

ABSTRACT

Purpose: This study was designed to identify pathogenic mutations causing autosomal recessive retinitis pigmentosa (RP) in consanguineous Pakistani families.

Methods: Two consanguineous families affected with autosomal recessive RP were identified from the Punjab Province of Pakistan. All affected individuals underwent a thorough ophthalmologic examination. Blood samples were collected, and genomic DNAs were extracted. Exclusion analysis was completed, and two-point LOD scores were calculated. Bidirectional sequencing of the β subunit of phosphodiesterase 6 (PDE6β) was completed.

Results: During exclusion analyses both families localized to chromosome 4p, harboring PDE6β, a gene previously associated with autosomal recessive RP. Sequencing of PDE6β identified missense mutations: c.1655G>A (p.R552Q) and c.1160C>T (p.P387L) in families PKRP161 and PKRP183, respectively. Bioinformatic analyses suggested that both mutations are deleterious for the native three-dimensional structure of the PDE6β protein.

Conclusions: These results strongly suggest that mutations in PDE6β are responsible for the disease phenotype in the consanguineous Pakistani families.

Show MeSH
Related in: MedlinePlus