title: Variations in Multiple Syndromic Deafness Genes Mimic Non-syndromic Hearing Loss.
abstract: The genetics of both syndromic (SHL) and non-syndromic hearing loss (NSHL) is characterized by a high degree of genetic heterogeneity. We analyzed whole exome sequencing data of 102 unrelated probands with apparently NSHL without a causative variant in known NSHL genes. We detected five causative variants in different SHL genes (SOX10, MITF, PTPN11, CHD7, and KMT2D) in five (4.9%) probands. Clinical re-evaluation of these probands shows that some of them have subtle syndromic findings, while none of them meets clinical criteria for the diagnosis of the associated syndrome (Waardenburg (SOX10 and MITF), Kallmann (CHD7 and SOX10), Noonan/LEOPARD (PTPN11), CHARGE (CHD7), or Kabuki (KMT2D). This study demonstrates that individuals who are evaluated for NSHL can have pathogenic variants in SHL genes that are not usually considered for etiologic studies.
authors: John P. Hussman Institute for Human Genomics, University of Miami, Miami, 33136, FL, USA.
authors: G
authors: G
authors: Bademci
authors: John P. Hussman Institute for Human Genomics, University of Miami, Miami, 33136, FL, USA.
authors: F B
authors: FB
authors: Cengiz
authors: John P. Hussman Institute for Human Genomics, University of Miami, Miami, 33136, FL, USA.
authors: J
authors: J
authors: Foster Ii
authors: Division of Genetics, Department of Pediatrics, Ankara University School of Medicine, Ankara, 06620, Turkey.
authors: D
authors: D
authors: Duman
authors: Department of Otolaryngology, Hacettepe University School of Medicine, Ankara, 06100, Turkey.
authors: L
authors: L
authors: Sennaroglu
authors: John P. Hussman Institute for Human Genomics, University of Miami, Miami, 33136, FL, USA.
authors: O
authors: O
authors: Diaz-Horta
authors: Division of Genetics, Department of Pediatrics, Ege University School of Medicine, Izmir, 35040, Turkey.
authors: T
authors: T
authors: Atik
authors: Department of Otolaryngology, Ege University School of Medicine, Izmir, 35040, Turkey.
authors: T
authors: T
authors: Kirazli
authors: Department of Otorhinolaryngology, Bozyaka Training and Research Hospital, Bozyaka, Izmir, 35170, Turkey.
authors: L
authors: L
authors: Olgun
authors: Department of Radiology, Ege University School of Medicine, Izmir, 35040, Turkey.
authors: H
authors: H
authors: Alper
authors: John P. Hussman Institute for Human Genomics, University of Miami, Miami, 33136, FL, USA.
authors: I
authors: I
authors: Menendez
authors: Koc University School of Medicine, Istanbul, 34450, Turkey.
authors: I
authors: I
authors: Loclar
authors: Department of Audiology, Hacettepe University Health Sciences Faculty, Ankara, 06100, Turkey.
authors: G
authors: G
authors: Sennaroglu
authors: Department of Audiology, Hacettepe University Health Sciences Faculty, Ankara, 06100, Turkey.
authors: S
authors: S
authors: Tokgoz-Yilmaz
authors: John P. Hussman Institute for Human Genomics, University of Miami, Miami, 33136, FL, USA.
authors: S
authors: S
authors: Guo
authors: Department of Otorhinolaryngology, Bozyaka Training and Research Hospital, Bozyaka, Izmir, 35170, Turkey.
authors: Y
authors: Y
authors: Olgun
authors: Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran.
authors: N
authors: N
authors: Mahdieh
authors: Faculty of Natural Sciences, Center of Excellence for Biodiversity, University of Tabriz, Tabriz, Iran.
authors: M
authors: M
authors: Bonyadi
authors: Department of Otolaryngology, Faculty of Medicine, Yuzuncu Yıl University, Van, 65080, Turkey.
authors: N
authors: N
authors: Bozan
authors: Department of Otolaryngology, Faculty of Medicine, Yuzuncu Yıl University, Van, 65080, Turkey.
authors: A
authors: A
authors: Ayral
authors: Division of Genetics, Department of Pediatrics, Ege University School of Medicine, Izmir, 35040, Turkey.
authors: F
authors: F
authors: Ozkinay
authors: Department of Otorhinolaryngology, Dicle University School of Medicine, Diyarbakir, 21280, Turkey.
authors: M
authors: M
authors: Yildirim-Baylan
authors: John P. Hussman Institute for Human Genomics, University of Miami, Miami, 33136, FL, USA.|Dr. John T. Macdonald Foundation Department of Human Genetics and Department of Otolaryngology, University of Miami, Miami, 33136, FL, USA.
authors: S H
authors: SH
authors: Blanton
authors: John P. Hussman Institute for Human Genomics, University of Miami, Miami, 33136, FL, USA.|Dr. John T. Macdonald Foundation Department of Human Genetics and Department of Otolaryngology, University of Miami, Miami, 33136, FL, USA.
authors: M
authors: M
authors: Tekin
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D017630:Connexins / Q000235:genetics*; D004265:DNA Helicases / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D003638:Deafness / Q000235:genetics*; D059472:Exome; D005260:Female; D018740:Genetic Heterogeneity; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D008297:Male; D051739:Microphthalmia-Associated Transcription Factor / Q000235:genetics; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics; D010375:Pedigree; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000235:genetics; D055757:SOXE Transcription Factors / Q000235:genetics; D013577:Syndrome
chemical_list: D017630:Connexins; D004268:DNA-Binding Proteins; C120898:KMT2D protein, human; C497234:MITF protein, human; D051739:Microphthalmia-Associated Transcription Factor; D009363:Neoplasm Proteins; C527923:SOX10 protein, human; D055757:SOXE Transcription Factors; C516724:PTPN11 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D004265:DNA Helicases; C491434:CHD7 protein, human