@article{BahenaDaftarianMaroofianetal.2022,
  author    = {Bahena, Paulina and Daftarian, Narsis and Maroofian, Reza and Linares, Paola and Villalobos, Daniel and Mirrahimi, Mehraban and Rad, Aboulfazl and Doll, Julia and Hofrichter, Michaela A. H. and Koparir, Asuman and R{\"o}der, Tabea and Han, Seungbin and Sabbaghi, Hamideh and Ahmadieh, Hamid and Behboudi, Hassan and Villanueva-Mendoza, Cristina and Cort{\´e}s-Gonzalez, Vianney and Zamora-Ortiz, Rocio and Kohl, Susanne and Kuehlewein, Laura and Darvish, Hossein and Alehabib, Elham and La Arenas-Sordo, Maria de Luz and Suri, Fatemeh and Vona, Barbara and Haaf, Thomas},
  title     = {Unraveling the genetic complexities of combined retinal dystrophy and hearing impairment},
  series = {Human Genetics},
  volume    = {141},
  journal   = {Human Genetics},
  number    = {3-4},
  issn      = {1432-1203},
  doi       = {10.1007/s00439-021-02303-1},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-267750},
  pages     = {785-803},
  year      = {2022},
  abstract  = {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 Alstr{\"o}m 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.},
  language  = {en}
}
@article{SemmlerSacconiBachetal.2014,
  author    = {Semmler, Anna-Lena and Sacconi, Sabrina and Bach, J. Elisa and Liebe, Claus and B{\"u}rmann, Jan and Kley, Rudolf A. and Ferbert, Andreas and Anderheiden, Roland and Van den Bergh, Peter and Martin, Jean-Jacques and De Jonghe, Peter and Neuen-Jacob, Eva and M{\"u}ller, Oliver and Deschauer, Marcus and Bergmann, Markus and Schr{\"o}der, J. Michael and Vorgerd, Matthias and Schulz, J{\"o}rg B. and Weis, Joachim and Kress, Wolfram and Claeys, Kristl G.},
  title     = {Unusual multisystemic involvement and a novel BAG3 mutation revealed by NGS screening in a large cohort of myofibrillar myopathies},
  series = {Orphanet Journal of Rare Diseases},
  volume    = {9},
  journal   = {Orphanet Journal of Rare Diseases},
  number    = {121},
  issn      = {1750-1172},
  doi       = {10.1186/s13023-014-0121-9},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-115623},
  year      = {2014},
  abstract  = {Background: Myofibrillar myopathies (MFM) are a group of phenotypically and genetically heterogeneous neuromuscular disorders, which are characterized by protein aggregations in muscle fibres and can be associated with multisystemic involvement. Methods: We screened a large cohort of 38 index patients with MFM for mutations in the nine thus far known causative genes using Sanger and next generation sequencing (NGS). We studied the clinical and histopathological characteristics in 38 index patients and five additional relatives (n = 43) and particularly focused on the associated multisystemic symptoms. Results: We identified 14 heterozygous mutations (diagnostic yield of 37\%), among them the novel p. Pro209Gln mutation in the BAG3 gene, which was associated with onset in adulthood, a mild phenotype and an axonal sensorimotor polyneuropathy, in the absence of giant axons at the nerve biopsy. We revealed several novel clinical phenotypes and unusual multisystemic presentations with previously described mutations: hearing impairment with a FLNC mutation, dysphonia with a mutation in DES and the first patient with a FLNC mutation presenting respiratory insufficiency as the initial symptom. Moreover, we described for the first time respiratory insufficiency occurring in a patient with the p. Gly154Ser mutation in CRYAB. Interestingly, we detected a polyneuropathy in 28\% of the MFM patients, including a BAG3 and a MYOT case, and hearing impairment in 13\%, including one patient with a FLNC mutation and two with mutations in the DES gene. In four index patients with a mutation in one of the MFM genes, typical histological findings were only identified at the ultrastructural level (29\%). Conclusions: We conclude that extraskeletal symptoms frequently occur in MFM, particularly cardiac and respiratory involvement, polyneuropathy and/or deafness. BAG3 mutations should be considered even in cases with a mild phenotype or an adult onset. We identified a genetic defect in one of the known genes in less than half of the MFM patients, indicating that more causative genes are still to be found. Next generation sequencing techniques should be helpful in achieving this aim.},
  language  = {en}
}