TY  - JOUR
A1  - Bahena, Paulina
A1  - Daftarian, Narsis
A1  - Maroofian, Reza
A1  - Linares, Paola
A1  - Villalobos, Daniel
A1  - Mirrahimi, Mehraban
A1  - Rad, Aboulfazl
A1  - Doll, Julia
A1  - Hofrichter, Michaela A. H.
A1  - Koparir, Asuman
A1  - Röder, Tabea
A1  - Han, Seungbin
A1  - Sabbaghi, Hamideh
A1  - Ahmadieh, Hamid
A1  - Behboudi, Hassan
A1  - Villanueva-Mendoza, Cristina
A1  - Cortés-Gonzalez, Vianney
A1  - Zamora-Ortiz, Rocio
A1  - Kohl, Susanne
A1  - Kuehlewein, Laura
A1  - Darvish, Hossein
A1  - Alehabib, Elham
A1  - La Arenas-Sordo, Maria de Luz
A1  - Suri, Fatemeh
A1  - Vona, Barbara
A1  - Haaf, Thomas
T1  - Unraveling the genetic complexities of combined retinal dystrophy and hearing impairment
JF  - Human Genetics
N2  - Usher syndrome, the most prevalent cause of combined hereditary vision and hearing impairment, is clinically and genetically heterogeneous. Moreover, several conditions with phenotypes overlapping Usher syndrome have been described. This makes the molecular diagnosis of hereditary deaf-blindness challenging. Here, we performed exome sequencing and analysis on 7 Mexican and 52 Iranian probands with combined retinal degeneration and hearing impairment (without intellectual disability). Clinical assessment involved ophthalmological examination and hearing loss questionnaire. Usher syndrome, most frequently due to biallelic variants in MYO7A (USH1B in 16 probands), USH2A (17 probands), and ADGRV1 (USH2C in 7 probands), was diagnosed in 44 of 59 (75%) unrelated probands. Almost half of the identified variants were novel. Nine of 59 (15%) probands displayed other genetic entities with dual sensory impairment, including Alström syndrome (3 patients), cone-rod dystrophy and hearing loss 1 (2 probands), and Heimler syndrome (1 patient). Unexpected findings included one proband each with Scheie syndrome, coenzyme Q10 deficiency, and pseudoxanthoma elasticum. In four probands, including three Usher cases, dual sensory impairment was either modified/aggravated or caused by variants in distinct genes associated with retinal degeneration and/or hearing loss. The overall diagnostic yield of whole exome analysis in our deaf-blind cohort was 92%. Two (3%) probands were partially solved and only 3 (5%) remained without any molecular diagnosis. In many cases, the molecular diagnosis is important to guide genetic counseling, to support prognostic outcomes and decisions with currently available and evolving treatment modalities.
KW  - Usher syndrome
KW  - hearing impairment
KW  - combined retinal dystrophy
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-267750
SN  - 1432-1203
VL  - 141
IS  - 3-4
ER  - 
TY  - JOUR
A1  - Weisschuh, Nicole
A1  - Mayer, Anja K.
A1  - Strom, Tim M.
A1  - Kohl, Susanne
A1  - Glöckle, Nicola
A1  - Schubach, Max
A1  - Andreasson, Sten
A1  - Bernd, Antje
A1  - Birch, David G.
A1  - Hamel, Christian P.
A1  - Heckenlively, John R.
A1  - Jacobson, Samuel G.
A1  - Kamme, Christina
A1  - Kellner, Ulrich
A1  - Kunstmann, Erdmute
A1  - Maffei, Pietro
A1  - Reiff, Charlotte M.
A1  - Rohrschneider, Klaus
A1  - Rosenberg, Thomas
A1  - Rudolph, Günther
A1  - Vámos, Rita
A1  - Varsányi, Balázs
A1  - Weleber, Richard G.
A1  - Wissinger, Bernd
T1  - Mutation Detection in Patients with Retinal Dystrophies Using Targeted Next Generation Sequencing
JF  - PLoS ONE
N2  - Retinal dystrophies (RD) constitute a group of blinding diseases that are characterized by clinical variability and pronounced genetic heterogeneity. The different nonsyndromic and syndromic forms of RD can be attributed to mutations in more than 200 genes. Consequently, next generation sequencing (NGS) technologies are among the most promising approaches to identify mutations in RD. We screened a large cohort of patients comprising 89 independent cases and families with various subforms of RD applying different NGS platforms. While mutation screening in 50 cases was performed using a RD gene capture panel, 47 cases were analyzed using whole exome sequencing. One family was analyzed using whole genome sequencing. A detection rate of 61% was achieved including mutations in 34 known and two novel RD genes. A total of 69 distinct mutations were identified, including 39 novel mutations. Notably, genetic findings in several families were not consistent with the initial clinical diagnosis. Clinical reassessment resulted in refinement of the clinical diagnosis in some of these families and confirmed the broad clinical spectrum associated with mutations in RD genes.
KW  - mutation detection
KW  - retinal dystrophies
KW  - next generation sequencing
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-167398
VL  - 11
IS  - 1
ER  -