Sequence variation within the RPGR gene: Evidence for a founder complex allele

In our study of sequence variation within the RPGR gene associated with X‐linked retinitis pigmentosa, we and others have observed a high rate of new mutation within this gene, as all reported mutations are unique or uncommon. In this article we report the identification in a single family of a comp...

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Bibliographic Details
Published in:Human mutation 2000-09, Vol.16 (3), p.273-274
Main Authors: Zito, Ilaria, Morris, Alex, Tyson, Phil, Winship, Ingrid, Sharp, Dianne, Gilbert, Dale, Thiselton, Dawn L., Bhattacharya, Shomi S., Hardcastle, Alison J.
Format: Article
Language:English
Subjects:
Alleles
Amino Acid Substitution - genetics
Base Sequence
Carrier Proteins - genetics
complex haplotype
Eye Proteins
Female
Founder Effect
Genetic Variation - genetics
Humans
linkage disequilbrium
Male
Pedigree
Retinitis Pigmentosa - genetics
retinitis pigmentosa GTPase regulator
RPGR
single nucleotide polymorphisms
SNPs
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Summary:In our study of sequence variation within the RPGR gene associated with X‐linked retinitis pigmentosa, we and others have observed a high rate of new mutation within this gene, as all reported mutations are unique or uncommon. In this article we report the identification in a single family of a complex allele of 7 sequence variants in linkage disequilibrium, of which four result in amino‐acid alterations (Arg425Lys, DGlu, Thr533Met and Gly566Glu). This complex allele was initially found in a family with XLRP. However, further study revealed an estimated prevalence of 4.3% (15/344 chromosomes) with this complex allele in the European population indicating the non‐pathogenic nature of this allele and, along with previously reported polymorphisms, further supporting a high level of human protein diversity for RPGR. This common complex allele may have been established in the population as a founder effect. Complete gene sequencing identified a potential pathogenic sequence variant in the family described (IVS6+5G>A). This study emphasises the need to create a more complete picture of the allelic variation within a gene, suggests cautious interpretation of a phenotypic association with variant sequences, and highlights the potential problems associated with interpreting genetic studies for diagnostic purposes. Hum Mutat 16:273–274, 2000. © 2000 Wiley‐Liss, Inc.
ISSN:1059-7794
1098-1004
DOI:10.1002/1098-1004(200009)16:3<273::AID-HUMU19>3.0.CO;2-W