Retinal dystrophy due to paternal isodisomy for chromosome 1 or chromosome 2, with homoallelism for mutations in RPE65 or MERTK, respectively

Am J Hum Genet. 2002 Jan;70(1):224-9. doi: 10.1086/338455. Epub 2001 Nov 27.


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.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Alleles
  • Carrier Proteins
  • Child
  • Child, Preschool
  • Chromosomes, Human, Pair 1 / genetics*
  • Chromosomes, Human, Pair 2 / genetics*
  • Eye Proteins / genetics
  • Female
  • Genomic Imprinting
  • Haplotypes / genetics
  • Heterozygote
  • Homozygote
  • Humans
  • Infant, Newborn
  • Male
  • Microsatellite Repeats / genetics
  • Middle Aged
  • Mutation / genetics*
  • Proteins / genetics*
  • Proto-Oncogene Proteins*
  • Receptor Protein-Tyrosine Kinases / genetics*
  • Retinal Degeneration / enzymology
  • Retinal Degeneration / genetics*
  • Retinal Degeneration / physiopathology
  • Retinitis Pigmentosa / enzymology
  • Retinitis Pigmentosa / genetics
  • Retinitis Pigmentosa / physiopathology
  • Uniparental Disomy / genetics*
  • c-Mer Tyrosine Kinase
  • cis-trans-Isomerases


  • Carrier Proteins
  • Eye Proteins
  • Proteins
  • Proto-Oncogene Proteins
  • MERTK protein, human
  • Receptor Protein-Tyrosine Kinases
  • c-Mer Tyrosine Kinase
  • retinoid isomerohydrolase
  • cis-trans-Isomerases