A variant form of Oguchi disease mapped to 13q34 associated with partial deletion of GRK1 gene

Qingjiong Zhang, Fareeha Zulfiqar, Sheikh Amer Riazuddin, Xueshan Xiao, Afshan Yasmeen, Peter K. Rogan, Raphael Caruso, Paul A. Sieving, Sheikh Riazuddin, J. Fielding Hejtmancik

Research output: Contribution to journalArticle

Abstract

Purpose: The purpose of this paper is to map the locus for a variant form of Oguchi disease in a Pakistani family and to identify the causative mutation. Methods: Family 61029 was ascertained in the Punjab province of Pakistan. It includes three 13- to 19-year-old patients with night blindness and 12 unaffected family members. A complete ophthalmological examination including fundus photography and electroretinography (ERG) was performed on each family member. A genome-wide scan was performed using microsatellite markers at about 10 cM intervals, and two-point lod scores were calculated. Polymerase chain reaction (PCR) cycle dideoxynucleotide sequencing was used to screen candidate genes inside the linked region for mutations and to delineate the deletion. Multiplex PCR and long template PCR were used to detect deletions and to define the size of deletions. Evaluation of fundus changes and ERG, lod score estimation, and identification of a mutation in the GRK1 gene were carried out. Results: All patients had night blindness since early childhood. Irregular coarse pigmentation was observed in the peripheral retina of each patient. The fundus appearance before and after 4 h of dark adaptation was similar except that the peripheral retinal pigmentary changes were slightly less evident after extended dark adaptation. Minimal or no rod function with normal cone function on ERG recordings were detected in all three affected members. The rod showed slow recovery to nearly normal amplitude after 4 h in the dark ERG in one individual but not in two other patients. A genomewide scan showed linkage only to D13S285. Fine mapping defined a region from D13S1315 to 13qter, with a lod score of 2.89 at θ=0 shown by D13S285 and 2.90 at θ=0 by the D13S261-D13S285-D13S1295-D13S293 haplotype. Analysis of the GRK1 gene, which is included in this interval, identified a c.827+623_883del mutation. This intragenic deletion cosegregates with the disease in the family and is only homozygous in affected individuals. This mutation was not detected in 96 controls. Conclusions: The retinal disease in the family reported here has several features differing from typical Oguchi disease, including an atypical Mizuo-Nakamura phenomenon and a non-recordable rod ERG even after 4 h of dark adaptation. Normal visual acuity, normal caliber of retinal blood vessels, and normal cone response on ERG recording suggest retinal dysfunction rather than degeneration (i.e., a variant form of Oguchi disease but unlikely to be retinitis pigmentosa). The disease in the Pakistani family localizes to 13q34 and is caused by a novel deletion including Exon 3 of the GRK1 gene.

Original languageEnglish (US)
Pages (from-to)977-985
Number of pages9
JournalMolecular Vision
Volume11
StatePublished - Nov 14 2005
Externally publishedYes

Fingerprint

Electroretinography
Gene Deletion
Lod Score
Dark Adaptation
Mutation
Night Blindness
Genes
Dideoxynucleotides
Retinal Diseases
Retinal Vessels
Polymerase Chain Reaction
Retinitis Pigmentosa
Photography
Multiplex Polymerase Chain Reaction
Pakistan
Pigmentation
Oguchi disease
Microsatellite Repeats
Haplotypes
Visual Acuity

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Zhang, Q., Zulfiqar, F., Riazuddin, S. A., Xiao, X., Yasmeen, A., Rogan, P. K., ... Hejtmancik, J. F. (2005). A variant form of Oguchi disease mapped to 13q34 associated with partial deletion of GRK1 gene. Molecular Vision, 11, 977-985.

A variant form of Oguchi disease mapped to 13q34 associated with partial deletion of GRK1 gene. / Zhang, Qingjiong; Zulfiqar, Fareeha; Riazuddin, Sheikh Amer; Xiao, Xueshan; Yasmeen, Afshan; Rogan, Peter K.; Caruso, Raphael; Sieving, Paul A.; Riazuddin, Sheikh; Hejtmancik, J. Fielding.

In: Molecular Vision, Vol. 11, 14.11.2005, p. 977-985.

Research output: Contribution to journalArticle

Zhang, Q, Zulfiqar, F, Riazuddin, SA, Xiao, X, Yasmeen, A, Rogan, PK, Caruso, R, Sieving, PA, Riazuddin, S & Hejtmancik, JF 2005, 'A variant form of Oguchi disease mapped to 13q34 associated with partial deletion of GRK1 gene', Molecular Vision, vol. 11, pp. 977-985.
Zhang Q, Zulfiqar F, Riazuddin SA, Xiao X, Yasmeen A, Rogan PK et al. A variant form of Oguchi disease mapped to 13q34 associated with partial deletion of GRK1 gene. Molecular Vision. 2005 Nov 14;11:977-985.
Zhang, Qingjiong ; Zulfiqar, Fareeha ; Riazuddin, Sheikh Amer ; Xiao, Xueshan ; Yasmeen, Afshan ; Rogan, Peter K. ; Caruso, Raphael ; Sieving, Paul A. ; Riazuddin, Sheikh ; Hejtmancik, J. Fielding. / A variant form of Oguchi disease mapped to 13q34 associated with partial deletion of GRK1 gene. In: Molecular Vision. 2005 ; Vol. 11. pp. 977-985.
@article{023662dca6844bfd956d874e72d398a2,
title = "A variant form of Oguchi disease mapped to 13q34 associated with partial deletion of GRK1 gene",
abstract = "Purpose: The purpose of this paper is to map the locus for a variant form of Oguchi disease in a Pakistani family and to identify the causative mutation. Methods: Family 61029 was ascertained in the Punjab province of Pakistan. It includes three 13- to 19-year-old patients with night blindness and 12 unaffected family members. A complete ophthalmological examination including fundus photography and electroretinography (ERG) was performed on each family member. A genome-wide scan was performed using microsatellite markers at about 10 cM intervals, and two-point lod scores were calculated. Polymerase chain reaction (PCR) cycle dideoxynucleotide sequencing was used to screen candidate genes inside the linked region for mutations and to delineate the deletion. Multiplex PCR and long template PCR were used to detect deletions and to define the size of deletions. Evaluation of fundus changes and ERG, lod score estimation, and identification of a mutation in the GRK1 gene were carried out. Results: All patients had night blindness since early childhood. Irregular coarse pigmentation was observed in the peripheral retina of each patient. The fundus appearance before and after 4 h of dark adaptation was similar except that the peripheral retinal pigmentary changes were slightly less evident after extended dark adaptation. Minimal or no rod function with normal cone function on ERG recordings were detected in all three affected members. The rod showed slow recovery to nearly normal amplitude after 4 h in the dark ERG in one individual but not in two other patients. A genomewide scan showed linkage only to D13S285. Fine mapping defined a region from D13S1315 to 13qter, with a lod score of 2.89 at θ=0 shown by D13S285 and 2.90 at θ=0 by the D13S261-D13S285-D13S1295-D13S293 haplotype. Analysis of the GRK1 gene, which is included in this interval, identified a c.827+623_883del mutation. This intragenic deletion cosegregates with the disease in the family and is only homozygous in affected individuals. This mutation was not detected in 96 controls. Conclusions: The retinal disease in the family reported here has several features differing from typical Oguchi disease, including an atypical Mizuo-Nakamura phenomenon and a non-recordable rod ERG even after 4 h of dark adaptation. Normal visual acuity, normal caliber of retinal blood vessels, and normal cone response on ERG recording suggest retinal dysfunction rather than degeneration (i.e., a variant form of Oguchi disease but unlikely to be retinitis pigmentosa). The disease in the Pakistani family localizes to 13q34 and is caused by a novel deletion including Exon 3 of the GRK1 gene.",
author = "Qingjiong Zhang and Fareeha Zulfiqar and Riazuddin, {Sheikh Amer} and Xueshan Xiao and Afshan Yasmeen and Rogan, {Peter K.} and Raphael Caruso and Sieving, {Paul A.} and Sheikh Riazuddin and Hejtmancik, {J. Fielding}",
year = "2005",
month = "11",
day = "14",
language = "English (US)",
volume = "11",
pages = "977--985",
journal = "Molecular Vision",
issn = "1090-0535",

}

TY - JOUR

T1 - A variant form of Oguchi disease mapped to 13q34 associated with partial deletion of GRK1 gene

AU - Zhang, Qingjiong

AU - Zulfiqar, Fareeha

AU - Riazuddin, Sheikh Amer

AU - Xiao, Xueshan

AU - Yasmeen, Afshan

AU - Rogan, Peter K.

AU - Caruso, Raphael

AU - Sieving, Paul A.

AU - Riazuddin, Sheikh

AU - Hejtmancik, J. Fielding

PY - 2005/11/14

Y1 - 2005/11/14

N2 - Purpose: The purpose of this paper is to map the locus for a variant form of Oguchi disease in a Pakistani family and to identify the causative mutation. Methods: Family 61029 was ascertained in the Punjab province of Pakistan. It includes three 13- to 19-year-old patients with night blindness and 12 unaffected family members. A complete ophthalmological examination including fundus photography and electroretinography (ERG) was performed on each family member. A genome-wide scan was performed using microsatellite markers at about 10 cM intervals, and two-point lod scores were calculated. Polymerase chain reaction (PCR) cycle dideoxynucleotide sequencing was used to screen candidate genes inside the linked region for mutations and to delineate the deletion. Multiplex PCR and long template PCR were used to detect deletions and to define the size of deletions. Evaluation of fundus changes and ERG, lod score estimation, and identification of a mutation in the GRK1 gene were carried out. Results: All patients had night blindness since early childhood. Irregular coarse pigmentation was observed in the peripheral retina of each patient. The fundus appearance before and after 4 h of dark adaptation was similar except that the peripheral retinal pigmentary changes were slightly less evident after extended dark adaptation. Minimal or no rod function with normal cone function on ERG recordings were detected in all three affected members. The rod showed slow recovery to nearly normal amplitude after 4 h in the dark ERG in one individual but not in two other patients. A genomewide scan showed linkage only to D13S285. Fine mapping defined a region from D13S1315 to 13qter, with a lod score of 2.89 at θ=0 shown by D13S285 and 2.90 at θ=0 by the D13S261-D13S285-D13S1295-D13S293 haplotype. Analysis of the GRK1 gene, which is included in this interval, identified a c.827+623_883del mutation. This intragenic deletion cosegregates with the disease in the family and is only homozygous in affected individuals. This mutation was not detected in 96 controls. Conclusions: The retinal disease in the family reported here has several features differing from typical Oguchi disease, including an atypical Mizuo-Nakamura phenomenon and a non-recordable rod ERG even after 4 h of dark adaptation. Normal visual acuity, normal caliber of retinal blood vessels, and normal cone response on ERG recording suggest retinal dysfunction rather than degeneration (i.e., a variant form of Oguchi disease but unlikely to be retinitis pigmentosa). The disease in the Pakistani family localizes to 13q34 and is caused by a novel deletion including Exon 3 of the GRK1 gene.

AB - Purpose: The purpose of this paper is to map the locus for a variant form of Oguchi disease in a Pakistani family and to identify the causative mutation. Methods: Family 61029 was ascertained in the Punjab province of Pakistan. It includes three 13- to 19-year-old patients with night blindness and 12 unaffected family members. A complete ophthalmological examination including fundus photography and electroretinography (ERG) was performed on each family member. A genome-wide scan was performed using microsatellite markers at about 10 cM intervals, and two-point lod scores were calculated. Polymerase chain reaction (PCR) cycle dideoxynucleotide sequencing was used to screen candidate genes inside the linked region for mutations and to delineate the deletion. Multiplex PCR and long template PCR were used to detect deletions and to define the size of deletions. Evaluation of fundus changes and ERG, lod score estimation, and identification of a mutation in the GRK1 gene were carried out. Results: All patients had night blindness since early childhood. Irregular coarse pigmentation was observed in the peripheral retina of each patient. The fundus appearance before and after 4 h of dark adaptation was similar except that the peripheral retinal pigmentary changes were slightly less evident after extended dark adaptation. Minimal or no rod function with normal cone function on ERG recordings were detected in all three affected members. The rod showed slow recovery to nearly normal amplitude after 4 h in the dark ERG in one individual but not in two other patients. A genomewide scan showed linkage only to D13S285. Fine mapping defined a region from D13S1315 to 13qter, with a lod score of 2.89 at θ=0 shown by D13S285 and 2.90 at θ=0 by the D13S261-D13S285-D13S1295-D13S293 haplotype. Analysis of the GRK1 gene, which is included in this interval, identified a c.827+623_883del mutation. This intragenic deletion cosegregates with the disease in the family and is only homozygous in affected individuals. This mutation was not detected in 96 controls. Conclusions: The retinal disease in the family reported here has several features differing from typical Oguchi disease, including an atypical Mizuo-Nakamura phenomenon and a non-recordable rod ERG even after 4 h of dark adaptation. Normal visual acuity, normal caliber of retinal blood vessels, and normal cone response on ERG recording suggest retinal dysfunction rather than degeneration (i.e., a variant form of Oguchi disease but unlikely to be retinitis pigmentosa). The disease in the Pakistani family localizes to 13q34 and is caused by a novel deletion including Exon 3 of the GRK1 gene.

UR - http://www.scopus.com/inward/record.url?scp=28044461491&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=28044461491&partnerID=8YFLogxK

M3 - Article

C2 - 16319817

AN - SCOPUS:28044461491

VL - 11

SP - 977

EP - 985

JO - Molecular Vision

JF - Molecular Vision

SN - 1090-0535

ER -