Evidence That the Penetrance of Mutations at the
RP11 Locus Causing Dominant Retinitis Pigmentosa
Is Influenced by a Gene Linked to the Homologous
RP11 Allele
T. L. McGee1, M. Devoto3,4,
J. Ott3, E. L. Berson2,
and T. P. Dryja1
1Ocular Molecular Genetics Institute, Massachusetts Eye and Ear Infirmary,
and
2Berman-Gund Laboratory for the Study of Retinal Degenerations,
Harvard Medical School, Boston;
3Laboratory of Statistical Genetics,
Rockefeller University, New York; and
4Laboratory of Molecular Genetics,
Instituto G. Gaslini, Genoa
American Journal of Human Genetics,
61: 1059-1066 (Nov 1997)
Abstract
A subset of families with autosomal dominant retinitis pigmentosa (RP)
display reduced penetrance with some asymptomatic gene carriers
showing no retinal abnormalities by ophthalmic examination or by
electroretinography. Here we describe a study of three families with
reduced-penetrance RP. In all three families the disease gene appears to
be linked to chromosome 19q13.4, the region containing the RP11 locus, as
defined by previously reported linkage studies based on five other
reduced-penetrance families. Meiotic recombinants in one of the newly
identified RP11 families and in two of the previously reported families serve
to restrict the disease locus to a 6-cM region bounded by markers
D19S572 and D19S926. We also compared the disease status of RP11
carriers with the segregation of microsatellite alleles within 19q13.4 from the
noncarrier parents in the newly reported and the previously reported
families. The results support the hypothesis that wild-type alleles at the
RP11 locus or at a closely linked locus inherited from the noncarrier parents
are a major factor influencing the penetrance of pathogenic alleles at this
locus.
