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Status: Bibliographieeintrag

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Verfasst von:Neuhaus, Christine [VerfasserIn]   i
 Rohrschneider, Klaus [VerfasserIn]   i
Titel:Next-generation sequencing reveals the mutational landscape of clinically diagnosed Usher syndrome
Titelzusatz:copy number variations, phenocopies, a predominant target for translational read-through, and PEX26 mutated in Heimler syndrome
Verf.angabe:Christine Neuhaus, Tobias Eisenberger, Christian Decker, Sandra Nagl, Cornelia Blank, Markus Pfister, Ingo Kennerknecht, Cornelie Müller‐Hofstede, Peter Charbel Issa, Raoul Heller, Bodo Beck, Klaus Rüther, Diana Mitter, Klaus Rohrschneider, Ute Steinhauer, Heike M. Korbmacher, Dagmar Huhle, Solaf M. Elsayed, Hesham M. Taha, Shahid M. Baig, Heidi Stöhr, Markus Preising, Susanne Markus, Fabian Moeller, Birgit Lorenz, Kerstin Nagel‐Wolfrum, Arif O. Khan & Hanno J. Bolz
E-Jahr:2017
Jahr:06 July 2017
Umfang:22 S.
Fussnoten:Gesehen am 26.10.2018
Titel Quelle:Enthalten in: Molecular genetics & genomic medicine
Ort Quelle:Chichester [u.a.] : Wiley, 2013
Jahr Quelle:2017
Band/Heft Quelle:5(2017), 5, Seite 531-552
ISSN Quelle:2324-9269
Abstract:Background: Combined retinal degeneration and sensorineural hearing impairment is mostly due to autosomal recessive Usher syndrome (USH1: congenital deafness, early retinitis pigmentosa (RP); USH2: progressive hearing impairment, RP). Methods: Sanger sequencing and NGS of 112 genes (Usher syndrome, nonsyndromic deafness, overlapping conditions), MLPA, and array-CGH were conducted in 138 patients clinically diagnosed with Usher syndrome. Results A molecular diagnosis was achieved in 97% of both USH1 and USH2 patients, with biallelic mutations in 97% (USH1) and 90% (USH2), respectively. Quantitative readout reliably detected CNVs (confirmed by MLPA or array-CGH), qualifying targeted NGS as one tool for detecting point mutations and CNVs. CNVs accounted for 10% of identified USH2A alleles, often in trans to seemingly monoallelic point mutations. We demonstrate PTC124-induced read-through of the common p.Trp3955* nonsense mutation (13% of detected USH2A alleles), a potential therapy target. Usher gene mutations were found in most patients with atypical Usher syndrome, but the diagnosis was adjusted in case of double homozygosity for mutations in OTOA and NR2E3, genes implicated in isolated deafness and RP. Two patients with additional enamel dysplasia had biallelic PEX26 mutations, for the first time linking this gene to Heimler syndrome. Conclusion: Targeted NGS not restricted to Usher genes proved beneficial in uncovering conditions mimicking Usher syndrome.
DOI:doi:10.1002/mgg3.312
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

kostenfrei: Volltext ; Verlag: http://dx.doi.org/10.1002/mgg3.312
 kostenfrei: Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1002/mgg3.312
 DOI: https://doi.org/10.1002/mgg3.312
Datenträger:Online-Ressource
Sprache:eng
Sach-SW:Copy number variation
 Heimler syndrome
 next-generation sequencing
 phenocopies
 translational read-through
 Usher syndrome
K10plus-PPN:1582325944
Verknüpfungen:→ Zeitschrift

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