title: AIPL1 implicated in the pathogenesis of two cases of autosomal recessive retinal degeneration.
abstract: OBJECTIVE
  To localize and identify the gene and mutations causing autosomal recessive retinal dystrophy in two consanguineous Pakistani families.
  
  
  METHODS
  Consanguineous families from Pakistan were ascertained to be affected with autosomal recessive retinal degeneration. All affected individuals underwent thorough ophthalmologic examinations. Blood samples were collected, and genomic DNA was extracted using a salting out procedure. Genotyping was performed using microsatellite markers spaced at approximately 10 cM intervals. Two-point linkage analysis was performed with the lod score method. Direct DNA sequencing of amplified genomic DNA was performed for mutation screening of candidate genes.
  
  
  RESULTS
  Genome-wide linkage scans yielded a lod score of 3.05 at θ=0 for D17S1832 and 3.82 at θ=0 for D17S938, localizing the disease gene to a 12.22 cM (6.64 Mb) region flanked by D17S1828 and D17S1852 for family 61032 and family 61227, which contains aryl hydrocarbon receptor interacting protein-like 1 (AIPL1), a gene previously implicated in recessive Leber congenital amaurosis and autosomal dominant cone-rod dystrophy. Sequencing of AIPL1 showed a homozygous c.773G>C (p.Arg258Pro) sequence change in all affected individuals of family 61032 and a homozygous c.465G>T (p.(H93_Q155del)) change in all affected members of family 61227.
  
  
  CONCLUSIONS
  The results strongly suggest that the c.773G>C (p.R258P) and c.465G>T (p.(H93_Q155del)) mutations in AIPL1 cause autosomal recessive retinal degeneration in these consanguineous Pakistani families.
authors.affiliation: Ophthalmic Genetics and Visual Function Branch, National Eye Institute, National Institutes of Health, Bethesda MD.
authors.forename: David
authors.initials: D
authors.lastname: Li
authors.affiliation: Ophthalmic Genetics and Visual Function Branch, National Eye Institute, National Institutes of Health, Bethesda MD ; Eye Center of the 2 Affiliated Hospital, Medical College of Zhejiang University, Hangzhou, China.
authors.forename: Chongfei
authors.initials: C
authors.lastname: Jin
authors.affiliation: Ophthalmic Genetics and Visual Function Branch, National Eye Institute, National Institutes of Health, Bethesda MD.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Jiao
authors.affiliation: Ophthalmic Genetics and Visual Function Branch, National Eye Institute, National Institutes of Health, Bethesda MD.
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.affiliation: National Centre of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan.
authors.forename: Tahmina
authors.initials: T
authors.lastname: Bushra
authors.affiliation: National Centre of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan.
authors.forename: Muhammad Asif
authors.initials: MA
authors.lastname: Naeem
authors.affiliation: Allama Iqbal Medical College, University of Health Sciences, Lahore Pakistan.
authors.forename: Nadeem H
authors.initials: NH
authors.lastname: Butt
authors.affiliation: National Centre of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan.
authors.forename: Tayyab
authors.initials: T
authors.lastname: Husnain
authors.affiliation: Ophthalmic Genetics and Visual Function Branch, National Eye Institute, National Institutes of Health, Bethesda MD.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Sieving
authors.affiliation: National Centre of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan ; Allama Iqbal Medical College, University of Health Sciences, Lahore Pakistan.
authors.forename: Sheikh
authors.initials: S
authors.lastname: Riazuddin
authors.affiliation: National Centre of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan ; The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore MD.
authors.forename: S Amer
authors.initials: SA
authors.lastname: Riazuddin
authors.affiliation: Ophthalmic Genetics and Visual Function Branch, National Eye Institute, National Institutes of Health, Bethesda MD.
authors.forename: J Fielding
authors.initials: JF
authors.lastname: Hejtmancik
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000595:Amino Acid Sequence; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics*; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D004596:Electroretinography; D005136:Eye Proteins / Q000737:chemistry / Q000235:genetics*; D005190:Family; D005260:Female; D005654:Fundus Oculi; D005808:Genes, Recessive / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008126:Lod Score; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D010154:Pakistan; D010375:Pedigree; D017434:Protein Structure, Tertiary; D022821:RNA Splice Sites / Q000235:genetics; D012162:Retinal Degeneration / Q000235:genetics*
chemical_list: C403625:AIPL1 protein, human; D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D005136:Eye Proteins; D022821:RNA Splice Sites