Mutation analysis in nephronophthisis using a combined approach of homozygosity mapping, CEL I endonuclease cleavage, and direct sequencing Communicated by Peter Byers
dc.contributor.author | Otto, Edgar A. | en_US |
dc.contributor.author | Helou, Juliana | en_US |
dc.contributor.author | Allen, Susan J. | en_US |
dc.contributor.author | O'Toole, John F. | en_US |
dc.contributor.author | Wise, Eric L. | en_US |
dc.contributor.author | Ashraf, Shazia | en_US |
dc.contributor.author | Attanasio, Massimo | en_US |
dc.contributor.author | Zhou, Weibin | en_US |
dc.contributor.author | Wolf, Matthias T. F. | en_US |
dc.contributor.author | Hildebrandt, Friedhelm | en_US |
dc.date.accessioned | 2008-03-06T19:11:50Z | |
dc.date.available | 2009-03-04T14:20:46Z | en_US |
dc.date.issued | 2008-03 | en_US |
dc.identifier.citation | Otto, Edgar A.; Helou, Juliana; Allen, Susan J.; O'Toole, John F.; Wise, Eric L.; Ashraf, Shazia; Attanasio, Massimo; Zhou, Weibin; Wolf, Matthias T.F.; Hildebrandt, Friedhelm (2008). "Mutation analysis in nephronophthisis using a combined approach of homozygosity mapping, CEL I endonuclease cleavage, and direct sequencing Communicated by Peter Byers ." Human Mutation 29(3): 418-426. <http://hdl.handle.net/2027.42/58034> | en_US |
dc.identifier.issn | 1059-7794 | en_US |
dc.identifier.issn | 1098-1004 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/58034 | |
dc.identifier.uri | http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=18076122&dopt=citation | |
dc.description.abstract | Nephronophthisis (NPHP), an autosomal recessive kidney disease, is the most frequent genetic cause of chronic renal failure in the first three decades of life. Mutations in eight genes ( NPHP1–8 ) have been identified. We here describe a combined approach for mutation screening of NPHP1 , NPHP2 , NPHP3 , NPHP4 , and NPHP5 in a worldwide cohort of 470 unrelated patients with NPHP. First, homozygous NPHP1 deletions were detected in 97 patients (21%) by multiplex PCR. Second, 25 patients with infantile NPHP were screened for mutations in inversin ( NPHP2/INVS ). We detected a novel compound heterozygous frameshift mutation (p.[Q485fs]+[R687fs]), and a homozygous nonsense mutation (p.R899X). Third, 37 patients presenting with NPHP and retinitis pigmentosa (Senior-LØken syndrome [SLS]) were screened for NPHP5/IQCB1 mutations by direct sequencing. We discovered five different (three novel) homozygous premature termination codon (PTC) mutations (p.F142fsX; p.R461X; p.R489X; p.W444X; and c.488–1G>A). The remaining 366 patients were further investigated for mutations in NPHP1 , NPHP3 , and NPHP4 . We applied a “homozygosity only” strategy and typed three highly polymorphic microsatellite markers at the respective loci. A total of 32, eight, and 14 patients showed homozygosity, and were screened by heteroduplex crude celery extract (CEL I) endonuclease digests. The sensitivity of CEL I was established as 92%, as it detected 73 out of 79 different known mutations simply on agarose gels. A total of 10 novel PTC mutations were found in NPHP1 (p.P186fs, p.R347X, p.V492fs, p.Y509X, and c.1884+1G>A), in NPHP3 (c.3812+2T>C and p.R1259X), and in NPHP4 (p.R59X, p.T1004fs, and p.V1091fs). The combined homozygosity mapping and CEL I endonuclease mutation analysis approach allowed us to identify rare mutations in a large cohort of patients at low cost. Hum Mutat 29(3), 418–426, 2008. © 2007 Wiley-Liss, Inc. | en_US |
dc.format.extent | 338365 bytes | |
dc.format.extent | 3118 bytes | |
dc.format.mimetype | application/pdf | |
dc.format.mimetype | text/plain | |
dc.publisher | Wiley Subscription Services, Inc., A Wiley Company | en_US |
dc.subject.other | Life and Medical Sciences | en_US |
dc.subject.other | Genetics | en_US |
dc.title | Mutation analysis in nephronophthisis using a combined approach of homozygosity mapping, CEL I endonuclease cleavage, and direct sequencing Communicated by Peter Byers | en_US |
dc.type | Article | en_US |
dc.rights.robots | IndexNoFollow | en_US |
dc.subject.hlbsecondlevel | Genetics | en_US |
dc.subject.hlbtoplevel | Health Sciences | en_US |
dc.subject.hlbtoplevel | Science | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.contributor.affiliationum | Department of Pediatrics, University of Michigan, Ann Arbor, Michigan | en_US |
dc.contributor.affiliationum | Department of Pediatrics, University of Michigan, Ann Arbor, Michigan | en_US |
dc.contributor.affiliationum | Department of Pediatrics, University of Michigan, Ann Arbor, Michigan | en_US |
dc.contributor.affiliationum | Department of Pediatrics, University of Michigan, Ann Arbor, Michigan | en_US |
dc.contributor.affiliationum | Department of Pediatrics, University of Michigan, Ann Arbor, Michigan | en_US |
dc.contributor.affiliationum | Department of Pediatrics, University of Michigan, Ann Arbor, Michigan | en_US |
dc.contributor.affiliationum | Department of Pediatrics, University of Michigan, Ann Arbor, Michigan | en_US |
dc.contributor.affiliationum | Department of Pediatrics, University of Michigan, Ann Arbor, Michigan | en_US |
dc.contributor.affiliationum | Department of Pediatrics, University of Michigan, Ann Arbor, Michigan | en_US |
dc.contributor.affiliationum | Department of Pediatrics, University of Michigan, Ann Arbor, Michigan ; Human Genetics, University of Michigan, Ann Arbor, Michigan ; University of Michigan Health System, 8220C MSRB III, 1150 West Medical Center Drive, Ann Arbor, MI | en_US |
dc.identifier.pmid | 18076122 | |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/58034/1/20669_ftp.pdf | |
dc.identifier.doi | http://dx.doi.org/10.1002/humu.20669 | en_US |
dc.identifier.source | Human Mutation | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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