title: Severe retinitis pigmentosa mapped to 4p15 and associated with a novel mutation in the PROM1 gene.
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 theta = 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.
authors.affiliation: Ophthalmic Genetics and Visual Function Branch, National Eye Institute, National Institutes of Health, Bethesda, MD 20982, USA. qingjiongzhang@yahoo.com
authors.forename: Qingjiong
authors.initials: Q
authors.lastname: Zhang
authors.forename: Fareeha
authors.initials: F
authors.lastname: Zulfiqar
authors.forename: Xueshan
authors.initials: X
authors.lastname: Xiao
authors.forename: S Amer
authors.initials: SA
authors.lastname: Riazuddin
authors.forename: Zahoor
authors.initials: Z
authors.lastname: Ahmad
authors.forename: Raphael
authors.initials: R
authors.lastname: Caruso
authors.forename: Ian
authors.initials: I
authors.lastname: MacDonald
authors.forename: Paul
authors.initials: P
authors.lastname: Sieving
authors.forename: Sheikh
authors.initials: S
authors.lastname: Riazuddin
authors.forename: J Fielding
authors.initials: JF
authors.lastname: Hejtmancik
mesh_terms: D000071916:AC133 Antigen; D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000235:genetics*; D001483:Base Sequence; D002874:Chromosome Mapping; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics*; D018389:Codon, Nonsense; D003241:Consanguinity; D004247:DNA / Q000235:genetics; D004596:Electroretinography; D005260:Female; D006023:Glycoproteins / Q000235:genetics*; D006239:Haplotypes; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008126:Lod Score; D008268:Macular Degeneration / Q000235:genetics / Q000473:pathology; D008297:Male; D010375:Pedigree; D010455:Peptides / Q000235:genetics*; D010641:Phenotype; D012174:Retinitis Pigmentosa / Q000235:genetics* / Q000473:pathology
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D018389:Codon, Nonsense; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; D004247:DNA