Kyle D Klingbeil1, Christopher M Greenland1, Selcuk Arslan2, Arianne Llamos Paneque3, Hakan Gurkan4, Selma Demir Ulusal4, Reza Maroofian5, Andrea Carrera-Gonzalez3, Stefany Montufar-Armendariz3, Rosario Paredes3, Nursel Elcioglu6, Ibis Menendez1, Mahdiyeh Behnam7, Joseph Foster1, Shengru Guo1, Sebastian Escarfuller1, Filiz Basak Cengiz1, Duygu Duman8, Guney Bademci1, Mustafa Tekin9. 1. John P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, FL, USA. 2. Karadeniz Technical University, Faculty of Medicine, Department of ENT, Trabzon, Turkey. 3. Medical Genetics Lab, FFAA Hospital, Quito, Ecuador. 4. Trakya University, School of Medicine, Department of Medical Genetics, Edirne, Turkey. 5. Institute of Biomedical and Clinical Science, University of Exeter Medical School, RILD Wellcome Wolfson Centre, Exeter, UK. 6. Department of Pediatric Genetics, Marmara University Medical School, Istanbul, Turkey. 7. Medical Genetics Laboratory of Genome, Isfahan, Iran. 8. Division of Genetics, Department of Pediatrics, Ankara University School of Medicine, Ankara, Turkey. 9. John P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, FL, USA; Dr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami, Miami, FL, USA. Electronic address: mtekin@med.miami.edu.
Abstract
INTRODUCTION: Branchio-oto-renal (BOR) syndrome is an autosomal dominant genetic disorder characterized by second branchial arch anomalies, hearing impairment, and renal malformations. Pathogenic mutations have been discovered in several genes such as EYA1, SIX5, and SIX1. However, nearly half of those affected reveal no pathogenic variant by traditional genetic testing. METHODS AND MATERIALS: Whole Exome sequencing and/or Sanger sequencing performed in 10 unrelated families from Turkey, Iran, Ecuador, and USA with BOR syndrome in this study. RESULTS: We identified causative DNA variants in six families including novel c.525delT, c.979T > C, and c.1768delG and a previously reported c.1779A > T variants in EYA1. Two large heterozygous deletions involving EYA1 were detected in additional two families. Whole exome sequencing did not reveal a causative variant in the remaining four families. CONCLUSIONS: A variety of DNA changes including large deletions underlie BOR syndrome in different populations, which can be detected with comprehensive genetic testing.
INTRODUCTION:Branchio-oto-renal (BOR) syndrome is an autosomal dominant genetic disorder characterized by second branchial arch anomalies, hearing impairment, and renal malformations. Pathogenic mutations have been discovered in several genes such as EYA1, SIX5, and SIX1. However, nearly half of those affected reveal no pathogenic variant by traditional genetic testing. METHODS AND MATERIALS: Whole Exome sequencing and/or Sanger sequencing performed in 10 unrelated families from Turkey, Iran, Ecuador, and USA with BOR syndrome in this study. RESULTS: We identified causative DNA variants in six families including novel c.525delT, c.979T > C, and c.1768delG and a previously reported c.1779A > T variants in EYA1. Two large heterozygous deletions involving EYA1 were detected in additional two families. Whole exome sequencing did not reveal a causative variant in the remaining four families. CONCLUSIONS: A variety of DNA changes including large deletions underlie BOR syndrome in different populations, which can be detected with comprehensive genetic testing.
Authors: J Weissenbach; G Gyapay; C Dib; A Vignal; J Morissette; P Millasseau; G Vaysseix; M Lathrop Journal: Nature Date: 1992-10-29 Impact factor: 49.962
Authors: S Kumar; W J Kimberling; A Lanyi; J Sumegi; J Pinnt; P Ing; S Tinley; H A Marres; C W Cremers Journal: Genomics Date: 1996-01-01 Impact factor: 5.736
Authors: Virginie S Vervoort; Richard J H Smith; Jane O'Brien; Richard Schroer; Albert Abbott; Roger E Stevenson; Charles E Schwartz Journal: Eur J Hum Genet Date: 2002-11 Impact factor: 4.246
Authors: A Chen; M Francis; L Ni; C W Cremers; W J Kimberling; Y Sato; P D Phelps; S C Bellman; M J Wagner; M Pembrey Journal: Am J Med Genet Date: 1995-09-25
Authors: C Stinckens; L Standaert; J W Casselman; P L Huygen; S Kumar; J Van de Wallen; C W Cremers Journal: Int J Pediatr Otorhinolaryngol Date: 2001-07-02 Impact factor: 1.675
Authors: S Abdelhak; V Kalatzis; R Heilig; S Compain; D Samson; C Vincent; D Weil; C Cruaud; I Sahly; M Leibovici; M Bitner-Glindzicz; M Francis; D Lacombe; J Vigneron; R Charachon; K Boven; P Bedbeder; N Van Regemorter; J Weissenbach; C Petit Journal: Nat Genet Date: 1997-02 Impact factor: 38.330
Authors: R J Smith; K B Coppage; J K Ankerstjerne; D T Capper; S Kumar; J Kenyon; S Tinley; K Comeau; W J Kimberling Journal: Genomics Date: 1992-12 Impact factor: 5.736
Authors: Niklas Krumm; Peter H Sudmant; Arthur Ko; Brian J O'Roak; Maika Malig; Bradley P Coe; Aaron R Quinlan; Deborah A Nickerson; Evan E Eichler Journal: Genome Res Date: 2012-05-14 Impact factor: 9.043
Authors: G Bademci; F B Cengiz; J Foster Ii; D Duman; L Sennaroglu; O Diaz-Horta; T Atik; T Kirazli; L Olgun; H Alper; I Menendez; I Loclar; G Sennaroglu; S Tokgoz-Yilmaz; S Guo; Y Olgun; N Mahdieh; M Bonyadi; N Bozan; A Ayral; F Ozkinay; M Yildirim-Baylan; S H Blanton; M Tekin Journal: Sci Rep Date: 2016-08-26 Impact factor: 4.379
Authors: Andre L P Tavares; Karyn Jourdeuil; Karen M Neilson; Himani D Majumdar; Sally A Moody Journal: Development Date: 2021-09-06 Impact factor: 6.862