I Moumoulidis1, P Axon, D Baguley, E Reid. 1. Department of Otolaryngology, University of Cambridge, Addenbrooke's Hospital, Hills Road, Cambridge, UK. moumoulidis@aol.com
Abstract
BACKGROUND: The aetiology of otosclerosis is not fully understood despite intensive research. It is, however, certain that a genetic component plays a significant role in the manifestation of otosclerosis, although the precise mode of inheritance is still uncertain. OBJECTIVE OF REVIEW: To provide an up-to-date review for the genetics of otosclerosis. The mode of inheritance, chromosomal and linkage studies are presented. In addition, the possible genetic relationship between otosclerosis and osteogenesis imperfecta, and the association between otosclerosis and specific human leucocyte antigen types are described. TYPE OF REVIEW: Systematic analysis of the literature was focused on any information related to the genetics of otosclerosis. SEARCH STRATEGY: A MEDLINE search (1960-2007) was undertaken to perform a comprehensive review. Articles were also identified through searches of the files of authors. RESULTS: The majority of epidemiological studies on families with otosclerosis suggest an autosomal dominant mode of inheritance with reduced penetrance of approximately 40%. Genetic linkage studies have demonstrated the presence of six loci (OTSC1, OTSC2, OTSC3, OTSC4, OTSC5 and OTSC7) located on chromosomes 15q, 7q, 6p, 16q, 3q and 6q respectively. Although these loci have been mapped, no causative genes have been identified, and we have little idea of the molecular process involved in this disease. While clinical similarities and some unreplicated genetic association studies suggest an aetiological relationship between otosclerosis and osteogenesis imperfecta-type I, there is no definite evidence of a common pathological process between the two diseases. CONCLUSIONS: Otosclerosis may be considered as a complex disease with relatively common monogenic forms. Knowledge of these genes could lead to substantial improvements in our ability to diagnose and possibly even prevent or treat this type of hearing deterioration.
BACKGROUND: The aetiology of otosclerosis is not fully understood despite intensive research. It is, however, certain that a genetic component plays a significant role in the manifestation of otosclerosis, although the precise mode of inheritance is still uncertain. OBJECTIVE OF REVIEW: To provide an up-to-date review for the genetics of otosclerosis. The mode of inheritance, chromosomal and linkage studies are presented. In addition, the possible genetic relationship between otosclerosis and osteogenesis imperfecta, and the association between otosclerosis and specific human leucocyte antigen types are described. TYPE OF REVIEW: Systematic analysis of the literature was focused on any information related to the genetics of otosclerosis. SEARCH STRATEGY: A MEDLINE search (1960-2007) was undertaken to perform a comprehensive review. Articles were also identified through searches of the files of authors. RESULTS: The majority of epidemiological studies on families with otosclerosis suggest an autosomal dominant mode of inheritance with reduced penetrance of approximately 40%. Genetic linkage studies have demonstrated the presence of six loci (OTSC1, OTSC2, OTSC3, OTSC4, OTSC5 and OTSC7) located on chromosomes 15q, 7q, 6p, 16q, 3q and 6q respectively. Although these loci have been mapped, no causative genes have been identified, and we have little idea of the molecular process involved in this disease. While clinical similarities and some unreplicated genetic association studies suggest an aetiological relationship between otosclerosis and osteogenesis imperfecta-type I, there is no definite evidence of a common pathological process between the two diseases. CONCLUSIONS:Otosclerosis may be considered as a complex disease with relatively common monogenic forms. Knowledge of these genes could lead to substantial improvements in our ability to diagnose and possibly even prevent or treat this type of hearing deterioration.
Authors: Allan Thomas Højland; Lisse J M Tavernier; Guy Van Camp; Erik Fransen; Isabelle Schrauwen; Manou Sommen; Vedat Topsakal; Isabelle Schatteman; Ingeborg Dhooge; Alex Huber; Diego Zanetti; Henricus P M Kunst; Alexander Hoischen; Michael B Petersen Journal: Hum Genet Date: 2021-08-19 Impact factor: 4.132
Authors: Susan G Stanton; Terry-Lynn Young; Nelly Abdelfatah; Ahmed A Mostafa; Curtis R French; Lance P Doucette; Cindy Penney; Matthew B Lucas; Anne Griffin; Valerie Booth; Christopher Rowley; Jessica E Besaw; Lisbeth Tranebjærg; Nanna Dahl Rendtorff; Kathy A Hodgkinson; Leichelle A Little; Sumit Agrawal; Lorne Parnes; Tony Batten; Susan Moore; Pingzhao Hu; Justin A Pater; Jim Houston; Dante Galutira; Tammy Benteau; Courtney MacDonald; Danielle French; Darren D O'Rielly Journal: Hum Genet Date: 2021-10-11 Impact factor: 5.881