PMID- 33136635
OWN - NLM
STAT- MEDLINE
DCOM- 20210728
LR  - 20230920
IS  - 1538-4667 (Electronic)
IS  - 0196-0202 (Linking)
VI  - 41
IP  - 6
DP  - 2020 Nov/Dec
TI  - Burden of Rare Variants in the OTOG Gene in Familial Meniere's Disease.
PG  - 1598-1605
LID - 10.1097/AUD.0000000000000878 [doi]
AB  - OBJECTIVES: Meniere's disease (MD) is a rare inner ear disorder characterized by 
      sensorineural hearing loss, episodic vertigo, and tinnitus. Familial MD has been 
      reported in 6 to 9% of sporadic cases, and few genes including FAM136A, DTNA, 
      PRKCB, SEMA3D, and DPT have been involved in single families, suggesting genetic 
      heterogeneity. In this study, the authors recruited 46 families with MD to search 
      for relevant candidate genes for hearing loss in familial MD. DESIGN: Exome 
      sequencing data from MD patients were analyzed to search for rare variants in 
      hearing loss genes in a case-control study. A total of 109 patients with MD (73 
      familial cases and 36 early-onset sporadic patients) diagnosed according to the 
      diagnostic criteria defined by the Barany Society were recruited in 11 hospitals. 
      The allelic frequencies of rare variants in hearing loss genes were calculated in 
      individuals with familial MD. A single rare variant analysis and a gene burden 
      analysis (GBA) were conducted in the dataset selecting 1 patient from each 
      family. Allelic frequencies from European and Spanish reference datasets were 
      used as controls. RESULTS: A total of 5136 single-nucleotide variants in hearing 
      loss genes were considered for single rare variant analysis in familial MD cases, 
      but only 1 heterozygous likely pathogenic variant in the OTOG gene (rs552304627) 
      was found in 2 unrelated families. The gene burden analysis found an enrichment 
      of rare missense variants in the OTOG gene in familial MD. So, 15 of 46 families 
      (33%) showed at least 1 rare missense variant in the OTOG gene, suggesting a key 
      role in familial MD. CONCLUSIONS: The authors found an enrichment of multiplex 
      rare missense variants in the OTOG gene in familial MD. This finding supports 
      OTOG as a relevant gene in familial MD and set the groundwork for genetic testing 
      in MD.
FAU - Roman-Naranjo, Pablo
AU  - Roman-Naranjo P
AD  - Otology & Neurotology Group CTS 495, Department of Genomic Medicine, Centro 
      Pfizer-Universidad de Granada-Junta de Andalucia de Genomica e Investigacion 
      Oncologica, Granada, Spain.
FAU - Gallego-Martinez, Alvaro
AU  - Gallego-Martinez A
AD  - Otology & Neurotology Group CTS 495, Department of Genomic Medicine, Centro 
      Pfizer-Universidad de Granada-Junta de Andalucia de Genomica e Investigacion 
      Oncologica, Granada, Spain.
FAU - Soto-Varela, Andres
AU  - Soto-Varela A
AD  - Division of Otoneurology, Department of Otorhinolaryngology, Complexo 
      Hospitalario Universitario, Santiago de Compostela, Spain.
FAU - Aran, Ismael
AU  - Aran I
AD  - Department of Otolaryngology, Complexo Hospitalario de Pontevedra, Pontevedra, 
      Spain.
FAU - Moleon, Maria Del Carmen
AU  - Moleon MDC
AD  - Department of Otolaryngology, Instituto de Investigacion Biosanitaria, 
      ibs.GRANADA, Hospital Universitario Virgen de las Nieves, Granada, Spain.
FAU - Espinosa-Sanchez, Juan Manuel
AU  - Espinosa-Sanchez JM
AD  - Department of Otolaryngology, Instituto de Investigacion Biosanitaria, 
      ibs.GRANADA, Hospital Universitario Virgen de las Nieves, Granada, Spain.
FAU - Amor-Dorado, Juan Carlos
AU  - Amor-Dorado JC
AD  - Department of Otolaryngology, Hospital Can Misses, Ibiza, Spain.
FAU - Batuecas-Caletrio, Angel
AU  - Batuecas-Caletrio A
AD  - Department of Otolaryngology, Hospital Universitario Salamanca, Instituto de 
      Investigacion Biomedica de Salamanca (IBSAL), Salamanca, Spain.
FAU - Perez-Vazquez, Paz
AU  - Perez-Vazquez P
AD  - Department of Otorhinolaryngology, Hospital Universitario de Cabuenes, Gijon, 
      Spain.
FAU - Lopez-Escamez, Jose Antonio
AU  - Lopez-Escamez JA
AD  - Otology & Neurotology Group CTS 495, Department of Genomic Medicine, Centro 
      Pfizer-Universidad de Granada-Junta de Andalucia de Genomica e Investigacion 
      Oncologica, Granada, Spain.
AD  - Department of Otolaryngology, Instituto de Investigacion Biosanitaria, 
      ibs.GRANADA, Hospital Universitario Virgen de las Nieves, Granada, Spain.
AD  - Department of Surgery, Division of Otolaryngology, Universidad de Granada, 
      Granada, Spain.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Ear Hear
JT  - Ear and hearing
JID - 8005585
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (OTOG protein, human)
SB  - IM
MH  - Case-Control Studies
MH  - Genetic Testing
MH  - *Hearing Loss, Sensorineural/genetics
MH  - Humans
MH  - Membrane Glycoproteins
MH  - *Meniere Disease/genetics
MH  - *Tinnitus
EDAT- 2020/11/03 06:00
MHDA- 2021/07/29 06:00
CRDT- 2020/11/02 17:12
PHST- 2020/11/02 17:12 [entrez]
PHST- 2020/11/03 06:00 [pubmed]
PHST- 2021/07/29 06:00 [medline]
AID - 00003446-202011000-00017 [pii]
AID - 10.1097/AUD.0000000000000878 [doi]
PST - ppublish
SO  - Ear Hear. 2020 Nov/Dec;41(6):1598-1605. doi: 10.1097/AUD.0000000000000878.