Retinal Dystrophy Due to Paternal Isodisomy for Chromosome 1 or Chromosome 2, with Homoallelism for Mutations in RPE65 or MERTK, Respectively
| Autor: | Samuel G. Jacobson, Christina L. McHenry, Andreas Gal, Julia E. Richards, Yun Li, Eberhard Schwinger, Debra A. Thompson, Mohammad Othman, Douglas Vollrath |
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| Rok vydání: | 2002 |
| Předmět: |
Adult
Male cis-trans-Isomerases Retinal degeneration Heterozygote Adolescent Biology C-Mer Tyrosine Kinase Genomic Imprinting 03 medical and health sciences Proto-Oncogene Proteins Report Retinitis pigmentosa medicine Genetics Humans Genetics(clinical) Child Eye Proteins Alleles Genetics (clinical) 030304 developmental biology 0303 health sciences c-Mer Tyrosine Kinase Homozygote Retinal Degeneration 030305 genetics & heredity Haplotype Infant Newborn Proteins Receptor Protein-Tyrosine Kinases Dystrophy Chromosome Middle Aged Uniparental Disomy MERTK medicine.disease Uniparental disomy Haplotypes Chromosomes Human Pair 1 Child Preschool Chromosomes Human Pair 2 Mutation Female Carrier Proteins Retinitis Pigmentosa Microsatellite Repeats |
| Zdroj: | The American Journal of Human Genetics. 70(1):224-229 |
| ISSN: | 0002-9297 |
| DOI: | 10.1086/338455 |
| Popis: | Uniparental disomy (UPD) is a rare condition in which a diploid offspring carries a chromosomal pair from a single parent. We now report the first two cases of UPD resulting in retinal degeneration. We identified an apparently homozygous loss-of-function mutation of RPE65 (1p31) in one retinal dystrophy patient and an apparently homozygous loss-of-function mutation of MERTK (2q14.1) in a second retinal dystrophy patient. In both families, the gene defect was present in the patient’s heterozygous father but not in the patient's mother. Analysis of haplotypes in each nuclear kindred, by use of DNA polymorphisms distributed along both chromosomal arms, indicated the absence of the maternal allele for all informative markers tested on chromosome 1 in the first patient and on chromosome 2 in the second patient. Our results suggest that retinal degeneration in these individuals is due to apparently complete paternal isodisomy involving reduction to homoallelism for RPE65 or MERTK loss-of-function alleles. Our findings provide evidence for the first time, in the case of chromosome 2, and confirm previous observations, in the case of chromosome 1, that there are no paternally imprinted genes on chromosomes 1 and 2 that have a major effect on phenotype. |
| Databáze: | OpenAIRE |
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