Severe retinitis pigmentosa mapped to 4p15 and associated with a novel mutation in the PROM1 gene |
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Authors: | Qingjiong Zhang Fareeha Zulfiqar Xueshan Xiao S Amer Riazuddin Zahoor Ahmad Raphael Caruso Ian MacDonald Paul Sieving Sheikh Riazuddin J Fielding Hejtmancik |
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Institution: | (1) Ophthalmic Genetics and Visual Function Branch, National Eye Institute, National Institutes of Health, Bethesda, MD 20982, USA;(2) State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, 54 Xianlie Road, Guangzhou, 510060, People’s Republic of China;(3) National Center of Excellence in Molecular Biology, University of Punjab, 87-West Canal Bank Road, Thokar Niaz Baig, Lahore, 53700, Pakistan;(4) OGCSB/NEI/NIH, Building 10, Room 10B10, 10 Center Drive, MSC 1860, Bethesda, MD 20892-1860, USA |
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Abstract: | Mutation in the PROM1 gene previously has been identified in one family with retinal degeneration for which neither ERG recordings
nor detailed information about visual impairment is available. A large family with multiple individuals affected by retinal
degeneration was ascertained in the Punjab province of Pakistan. The visual acuity of all affected patients in the family
was severely compromised beginning in early childhood. The retinal disease in this family is a severe form of retinitis pigmentosa
(RP) accompanied by macular degeneration. Fundus changes advanced with age. Choriocapillaris atrophy and posterior RPE atrophy
were obvious allowing visualization of the large choroidal vessels in patients over 40 years of age. Rod and cone responses
on ERG recordings were extinguished in patient’s teens. A genome-wide scan mapped the disease to a 34.7 cM region of chromosome
4p14–p16 between D4S1599 and D4S405. A maximum lod score of 3.96 with D4S403 and D4S391 is seen at θ = 0. Sequence analysis
of PROM1 located in the linkage interval identified a c.1726C>T homozygous transition in exon 15: resulting in p.Gln576X in
the translated protein. This mutation is found in a homozygous state in all six affected individuals and was heterozygous
in five of the six unaffected family members examined. The mutation was not detected in 192 chromosomes of unrelated control
individuals of the same ethnicity and from the same region. This delineates the phenotypic characteristics of retinopathy
caused by mutations in PROM1.
Qingjiong Zhang, Fareeha Zulfiqar, Xueshan Xiao, Sheikh Riazuddin and J. Fielding Hejtmancik contributed equally. |
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