@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{VonaMaroofianBellacchioetal.2018,
  author    = {Vona, Barbara and Maroofian, Reza and Bellacchio, Emanuele and Najafi, Maryam and Thompson, Kyle and Alahmad, Ahmad and He, Langping and Ahangari, Najmeh and Rad, Abolfazl and Shahrokhzadeh, Sima and Bahena, Paulina and Mittag, Falk and Traub, Frank and Movaffagh, Jebrail and Amiri, Nafise and Doosti, Mohammad and Boostani, Reza and Shirzadeh, Ebrahim and Haaf, Thomas and Diodato, Daria and Schmidts, Miriam and Taylor, Robert W. and Karimiani, Ehsan Ghayoor},
  title     = {Expanding the clinical phenotype of IARS2-related mitochondrial disease},
  series = {BMC Medical Genetics},
  volume    = {19},
  journal   = {BMC Medical Genetics},
  number    = {196},
  doi       = {10.1186/s12881-018-0709-3},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-176620},
  year      = {2018},
  abstract  = {Background: IARS2 encodes a mitochondrial isoleucyl-tRNA synthetase, a highly conserved nuclear-encoded enzyme required for the charging of tRNAs with their cognate amino acid for translation. Recently, pathogenic IARS2 variants have been identified in a number of patients presenting broad clinical phenotypes with autosomal recessive inheritance. These phenotypes range from Leigh and West syndrome to a new syndrome abbreviated CAGSSS that is characterised by cataracts, growth hormone deficiency, sensory neuropathy, sensorineural hearing loss, and skeletal dysplasia, as well as cataract with no additional anomalies. Methods: Genomic DNA from Iranian probands from two families with consanguineous parental background and overlapping CAGSSS features were subjected to exome sequencing and bioinformatics analysis. Results: Exome sequencing and data analysis revealed a novel homozygous missense variant (c.2625C > T, p.Pro909Ser, NM_018060.3) within a 14.3 Mb run of homozygosity in proband 1 and a novel homozygous missense variant (c.2282A > G, p.His761Arg) residing in an ~ 8 Mb region of homozygosity in a proband of the second family. Patient-derived fibroblasts from proband 1 showed normal respiratory chain enzyme activity, as well as unchanged oxidative phosphorylation protein subunits and IARS2 levels. Homology modelling of the known and novel amino acid residue substitutions in IARS2 provided insight into the possible consequence of these variants on function and structure of the protein. Conclusions: This study further expands the phenotypic spectrum of IARS2 pathogenic variants to include two patients (patients 2 and 3) with cataract and skeletal dysplasia and no other features of CAGSSS to the possible presentation of the defects in IARS2. Additionally, this study suggests that adult patients with CAGSSS may manifest central adrenal insufficiency and type II esophageal achalasia and proposes that a variable sensorineural hearing loss onset, proportionate short stature, polyneuropathy, and mild dysmorphic features are possible, as seen in patient 1. Our findings support that even though biallelic IARS2 pathogenic variants can result in a distinctive, clinically recognisable phenotype in humans, it can also show a wide range of clinical presentation from severe pediatric neurological disorders of Leigh and West syndrome to both non-syndromic cataract and cataract accompanied by skeletal dysplasia.},
  language  = {en}
}