Neuhaus, Christine, Eisenberger, Tobias, Decker, Christian, Nagl, Sandra, Blank, Cornelia, Pfister, Markus, Kennerknecht, Ingo, Mueller-Hofstede, Cornelie, Issa, Peter Charbel ORCID: 0000-0002-0351-6673, Heller, Raoul, Beck, Bodo, Ruether, Klaus, Mitter, Diana, Rohrschneider, Klaus, Steinhauer, Ute, Korbmacher, Heike M., Huhle, Dagmar, Elsayed, Solaf M., Taha, Hesham M., Baig, Shahid M., Stoehr, Heidi, Preising, Markus, Markus, Susanne, Moeller, Fabian, Lorenz, Birgit, Nagel-Wolfrum, Kerstin, Khan, Arif O. and Bolz, Hanno J. (2017). Next-generation sequencing reveals the mutational landscape of clinically diagnosed Usher syndrome: copy number variations, phenocopies, a predominant target for translational read-through, and PEX26 mutated in Heimler syndrome. Mol. Genet. Genom. Med., 5 (5). S. 531 - 553. HOBOKEN: WILEY. ISSN 2324-9269

Full text not available from this repository.

Abstract

BackgroundCombined 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). MethodsSanger 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. ResultsA 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. ConclusionTargeted NGS not restricted to Usher genes proved beneficial in uncovering conditions mimicking Usher syndrome.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Neuhaus, ChristineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Eisenberger, TobiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Decker, ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nagl, SandraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Blank, CorneliaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pfister, MarkusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kennerknecht, IngoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mueller-Hofstede, CornelieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Issa, Peter CharbelUNSPECIFIEDorcid.org/0000-0002-0351-6673UNSPECIFIED
Heller, RaoulUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Beck, BodoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ruether, KlausUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mitter, DianaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rohrschneider, KlausUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Steinhauer, UteUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Korbmacher, Heike M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Huhle, DagmarUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Elsayed, Solaf M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Taha, Hesham M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Baig, Shahid M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stoehr, HeidiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Preising, MarkusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Markus, SusanneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Moeller, FabianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lorenz, BirgitUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nagel-Wolfrum, KerstinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Khan, Arif O.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bolz, Hanno J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-221003
DOI: 10.1002/mgg3.312
Journal or Publication Title: Mol. Genet. Genom. Med.
Volume: 5
Number: 5
Page Range: S. 531 - 553
Date: 2017
Publisher: WILEY
Place of Publication: HOBOKEN
ISSN: 2324-9269
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
PEROXISOME-BIOGENESIS DISORDERS; SYNDROME TYPE IIA; MYOSIN VIIA GENE; S-CONE-SYNDROME; RETINITIS-PIGMENTOSA; USH2A GENE; MOLECULAR DIAGNOSIS; HEARING-LOSS; INFANTILE HYPERINSULINISM; CONTIGUOUS GENEMultiple languages
Genetics & HeredityMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/22100

Downloads

Downloads per month over past year

Altmetric

Export

Actions (login required)

View Item View Item