Abstract:
: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.
journal_name
Am J Hum Genetjournal_title
American journal of human geneticsauthors
Thompson DA,McHenry CL,Li Y,Richards JE,Othman MI,Schwinger E,Vollrath D,Jacobson SG,Gal Adoi
10.1086/338455subject
Has Abstractpub_date
2002-01-01 00:00:00pages
224-9issue
1eissn
0002-9297issn
1537-6605pii
S0002-9297(07)61295-6journal_volume
70pub_type
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