Abstract
PURPOSE. To determine whether genomic rearrangements in the PRPF31 (RP11) gene are a frequent cause of autosomal dominant retinitis pigmentosa (adRP) in a cohort of patients with adRP. METHODS. In a cohort of 200 families with adRP, disease-causing mutations have previously been identified in 107 families. To determine the cause of disease in the remaining families, linkage testing was performed with markers for 13 known adRP loci. In a large American family, evidence was found of linkage to the PRPF31 gene, although DNA sequencing revealed no mutations. SNP testing throughout the genomic region was used to determine whether any part of the gene was deleted. Aberrant segregation of a SNP near exon 1 was observed, leading to the testing of additional SNPs in the region. After identifying an insertion-deletion mutation, the remaining 92 families were screened for genomic rearrangements in PRPF31 with multiplex ligation-dependent probe amplification (MLPA). RESULTS. Five unique rearrangements were identified in the 93 families tested. In the large family used for linkage exclusion testing, an insertion-deletion was found that disrupts exon 1. The other four mutations identified in the cohort were deletions, ranging from 5 kb to greater than 45 kb. Two of the large deletions encompass all PRPF31 as well as several adjacent genes. The two smaller deletions involve either 5 or 10 completely deleted exons. CONCLUSIONS. In an earlier long-term study of 200 families with adRP, disease-causing mutations were identified in 53% of the families. Mutation-testing by sequencing missed large-scale genomic rearrangements such as insertions or deletions. MLPA was used to identify genomic rearrangements in PRPF31 in five families, suggesting a frequency of approximately 2.5%. Mutations in PRPF31 now account for 8% of this adRP cohort.
| Original language | English |
|---|---|
| Pages (from-to) | 4579-4588 |
| Number of pages | 10 |
| Journal | Investigative Ophthalmology and Visual Science |
| Volume | 47 |
| Issue number | 10 |
| DOIs | |
| State | Published - Oct 1 2006 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Ophthalmology
Cite this
Genomic rearrangements of the PRPF31 gene account for 2.5% of autosomal dominant retinitis pigmentosa. / Sullivan, Lori S.; Bowne, Sara J.; Seaman, C. Robyn; Blanton, Susan H; Lewis, Richard A.; Heckenlively, John R.; Birch, David G.; Hughbanks-Wheaton, Dianna; Daiger, Stephen P.
In: Investigative Ophthalmology and Visual Science, Vol. 47, No. 10, 01.10.2006, p. 4579-4588.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Genomic rearrangements of the PRPF31 gene account for 2.5% of autosomal dominant retinitis pigmentosa
AU - Sullivan, Lori S.
AU - Bowne, Sara J.
AU - Seaman, C. Robyn
AU - Blanton, Susan H
AU - Lewis, Richard A.
AU - Heckenlively, John R.
AU - Birch, David G.
AU - Hughbanks-Wheaton, Dianna
AU - Daiger, Stephen P.
PY - 2006/10/1
Y1 - 2006/10/1
N2 - PURPOSE. To determine whether genomic rearrangements in the PRPF31 (RP11) gene are a frequent cause of autosomal dominant retinitis pigmentosa (adRP) in a cohort of patients with adRP. METHODS. In a cohort of 200 families with adRP, disease-causing mutations have previously been identified in 107 families. To determine the cause of disease in the remaining families, linkage testing was performed with markers for 13 known adRP loci. In a large American family, evidence was found of linkage to the PRPF31 gene, although DNA sequencing revealed no mutations. SNP testing throughout the genomic region was used to determine whether any part of the gene was deleted. Aberrant segregation of a SNP near exon 1 was observed, leading to the testing of additional SNPs in the region. After identifying an insertion-deletion mutation, the remaining 92 families were screened for genomic rearrangements in PRPF31 with multiplex ligation-dependent probe amplification (MLPA). RESULTS. Five unique rearrangements were identified in the 93 families tested. In the large family used for linkage exclusion testing, an insertion-deletion was found that disrupts exon 1. The other four mutations identified in the cohort were deletions, ranging from 5 kb to greater than 45 kb. Two of the large deletions encompass all PRPF31 as well as several adjacent genes. The two smaller deletions involve either 5 or 10 completely deleted exons. CONCLUSIONS. In an earlier long-term study of 200 families with adRP, disease-causing mutations were identified in 53% of the families. Mutation-testing by sequencing missed large-scale genomic rearrangements such as insertions or deletions. MLPA was used to identify genomic rearrangements in PRPF31 in five families, suggesting a frequency of approximately 2.5%. Mutations in PRPF31 now account for 8% of this adRP cohort.
AB - PURPOSE. To determine whether genomic rearrangements in the PRPF31 (RP11) gene are a frequent cause of autosomal dominant retinitis pigmentosa (adRP) in a cohort of patients with adRP. METHODS. In a cohort of 200 families with adRP, disease-causing mutations have previously been identified in 107 families. To determine the cause of disease in the remaining families, linkage testing was performed with markers for 13 known adRP loci. In a large American family, evidence was found of linkage to the PRPF31 gene, although DNA sequencing revealed no mutations. SNP testing throughout the genomic region was used to determine whether any part of the gene was deleted. Aberrant segregation of a SNP near exon 1 was observed, leading to the testing of additional SNPs in the region. After identifying an insertion-deletion mutation, the remaining 92 families were screened for genomic rearrangements in PRPF31 with multiplex ligation-dependent probe amplification (MLPA). RESULTS. Five unique rearrangements were identified in the 93 families tested. In the large family used for linkage exclusion testing, an insertion-deletion was found that disrupts exon 1. The other four mutations identified in the cohort were deletions, ranging from 5 kb to greater than 45 kb. Two of the large deletions encompass all PRPF31 as well as several adjacent genes. The two smaller deletions involve either 5 or 10 completely deleted exons. CONCLUSIONS. In an earlier long-term study of 200 families with adRP, disease-causing mutations were identified in 53% of the families. Mutation-testing by sequencing missed large-scale genomic rearrangements such as insertions or deletions. MLPA was used to identify genomic rearrangements in PRPF31 in five families, suggesting a frequency of approximately 2.5%. Mutations in PRPF31 now account for 8% of this adRP cohort.
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UR - http://www.scopus.com/inward/citedby.url?scp=33750593210&partnerID=8YFLogxK
U2 - 10.1167/iovs.06-0440
DO - 10.1167/iovs.06-0440
M3 - Article
C2 - 17003455
AN - SCOPUS:33750593210
VL - 47
SP - 4579
EP - 4588
JO - Investigative Ophthalmology and Visual Science
JF - Investigative Ophthalmology and Visual Science
SN - 0146-0404
IS - 10
ER -