Genomewide homozygosity mapping and molecular analysis of a candidate gene located on 22q13 (fibulin-1) in a previously undescribed vitreoretinal dystrophy.
OBJECTIVE
To localize the gene that causes an autosomal recessively inherited vitreoretinal dystrophy that has not been described, to our knowledge, and to analyze a candidate gene mapped to 22q13 (fibulin-1 [FBLN1]).


METHODS
Homozygosity mapping with 500 microsatellite markers spread over the whole genome (mean distance, 7.2 centimorgans [cM]) and mutation analysis of the complete coding region of FBLN1.


RESULTS
Homozygosity for all analyzed markers was found in the 4 affected siblings in a region on chromosome 22 encompassing 12 cM from D22S444 (centromeric) to D22S1170 (telomeric). Lod scores were between 0.017 and 2.36 (theta = 0). A mutation analysis of the complete coding region of FBLN1, which encodes interacting extracellular matrix proteins, revealed 4 previously undescribed single nucleotide polymorphisms.


CONCLUSIONS
A genomewide homozygosity mapping analysis supported the hypothesis that the gene responsible for a unique vitreoretinal dystrophy is located on chromosome 22q13. No obviously pathogenic mutation was found in the candidate gene, FBLN1.
Weigell-Weber
Maike
M
Institute of Medical Genetics, University of Zurich, Switzerland.
Sarra
Gian-Marco
GM
Kotzot
Dieter
D
Sandkuijl
Lodewijk
L
Messmer
Elmar
E
Hergersberg
Martin
M
D000368:Aged; D001483:Base Sequence; D002135:Calcium-Binding Proteins / Q000235:genetics*; D002874:Chromosome Mapping; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics*; D004252:DNA Mutational Analysis; D016326:Extracellular Matrix Proteins / Q000235:genetics; D015785:Eye Diseases, Hereditary / Q000235:genetics* / Q000473:pathology; D005260:Female; D005808:Genes, Recessive; D006239:Haplotypes; D006720:Homozygote; D006801:Humans; D008126:Lod Score; D008297:Male; D018895:Microsatellite Repeats; D008967:Molecular Biology; D008969:Molecular Sequence Data; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D012162:Retinal Degeneration / Q000235:genetics* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014822:Vitreous Body / Q000473:pathology*
D002135:Calcium-Binding Proteins; D016326:Extracellular Matrix Proteins; C060820:fibulin