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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.

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Related in: MedlinePlus

Fundus photographs of affected individuals of families PKFP161 and PKRP183. A: OD and OS of affected individual 17 of PKRP161 (age: 28 years). B: OD and OS of affected individual 7 of PKRP183 (age: 55 years). C: OD and OS of unaffected individual 19 of PKRP183 (age: 51 years). Photographs show peripheral fundus demonstrating several features associated with RP including a waxy pallor of the optic disc, attenuated arterioles and peripheral bone spicules. Visual acuity were recorded as 6/24, 6/24 (OD, OS) and 6/18, 6/18 (OD, OS) for individual 17 of PKRP161 and individual 7 of PKRP183, respectively. OD: Oculus Dexter (right eye); and OS: Oculus Sinister (left eye).
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f2: Fundus photographs of affected individuals of families PKFP161 and PKRP183. A: OD and OS of affected individual 17 of PKRP161 (age: 28 years). B: OD and OS of affected individual 7 of PKRP183 (age: 55 years). C: OD and OS of unaffected individual 19 of PKRP183 (age: 51 years). Photographs show peripheral fundus demonstrating several features associated with RP including a waxy pallor of the optic disc, attenuated arterioles and peripheral bone spicules. Visual acuity were recorded as 6/24, 6/24 (OD, OS) and 6/18, 6/18 (OD, OS) for individual 17 of PKRP161 and individual 7 of PKRP183, respectively. OD: Oculus Dexter (right eye); and OS: Oculus Sinister (left eye).

Mentions: The families described in this study, PKRP161 and PKRP183, are from the Punjab province of Pakistan (Figure 1). All affected individuals underwent a thorough ophthalmologic examination that concluded that all affected individuals in the two families fulfill the diagnostic criteria of RP. Affected patients presented symptoms of night blindness in early childhood. Fundus examination of affected patients illustrated cardinal features of RP, namely arteriolar constriction, waxy pallor optic disc, and pigmentation on the peripheral as well as central retina (Figure 2). ERG recordings showed absence of both rod and cone responses; scotopic and photopic ERG responses were highly reduced or absent (Figure 3).


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)

Fundus photographs of affected individuals of families PKFP161 and PKRP183. A: OD and OS of affected individual 17 of PKRP161 (age: 28 years). B: OD and OS of affected individual 7 of PKRP183 (age: 55 years). C: OD and OS of unaffected individual 19 of PKRP183 (age: 51 years). Photographs show peripheral fundus demonstrating several features associated with RP including a waxy pallor of the optic disc, attenuated arterioles and peripheral bone spicules. Visual acuity were recorded as 6/24, 6/24 (OD, OS) and 6/18, 6/18 (OD, OS) for individual 17 of PKRP161 and individual 7 of PKRP183, respectively. OD: Oculus Dexter (right eye); and OS: Oculus Sinister (left eye).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f2: Fundus photographs of affected individuals of families PKFP161 and PKRP183. A: OD and OS of affected individual 17 of PKRP161 (age: 28 years). B: OD and OS of affected individual 7 of PKRP183 (age: 55 years). C: OD and OS of unaffected individual 19 of PKRP183 (age: 51 years). Photographs show peripheral fundus demonstrating several features associated with RP including a waxy pallor of the optic disc, attenuated arterioles and peripheral bone spicules. Visual acuity were recorded as 6/24, 6/24 (OD, OS) and 6/18, 6/18 (OD, OS) for individual 17 of PKRP161 and individual 7 of PKRP183, respectively. OD: Oculus Dexter (right eye); and OS: Oculus Sinister (left eye).
Mentions: The families described in this study, PKRP161 and PKRP183, are from the Punjab province of Pakistan (Figure 1). All affected individuals underwent a thorough ophthalmologic examination that concluded that all affected individuals in the two families fulfill the diagnostic criteria of RP. Affected patients presented symptoms of night blindness in early childhood. Fundus examination of affected patients illustrated cardinal features of RP, namely arteriolar constriction, waxy pallor optic disc, and pigmentation on the peripheral as well as central retina (Figure 2). ERG recordings showed absence of both rod and cone responses; scotopic and photopic ERG responses were highly reduced or absent (Figure 3).

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