Further audiovestibular characterization of DFNB77, caused by deleterious variants in LOXHD1, and investigation into the involvement of Fuchs corneal dystrophy

Autor: Vivian Schreur, Margit Schraders, Ilse Feenstra, J.M. van de Kamp, M. J. van den Boogaard, Henricus P. M. Kunst, Mariet W. Elting, Carel B. Hoyng, Ronald J.E. Pennings, Mieke Wesdorp, Hannie Kremer, Ronald J.C. Admiraal, Andy J. Beynon, Helger G. Yntema, Jaap Oostrik
Přispěvatelé: Human genetics, AGEM - Endocrinology, metabolism and nutrition, AGEM - Inborn errors of metabolism, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Reproduction & Development (AR&D)
Rok vydání: 2018
Předmět:
0301 basic medicine
Adult
Male
DFNB77
Heterozygote
hereditary hearing impairment
Adolescent
Genotype
genotype-phenotype correlations
Hearing Loss
Sensorineural
Mutation
Missense
Intrafamilial variation
Biology
Sensory disorders Donders Center for Medical Neuroscience [Radboudumc 12]
03 medical and health sciences
All institutes and research themes of the Radboud University Medical Center
0302 clinical medicine
Audiometry
Fuchs corneal dystrophy
Genetics
Missense mutation
Humans
Genetic Predisposition to Disease
Genetics(clinical)
Child
Genotype-Phenotype Correlations
Genetics (clinical)
Genetic Association Studies
LOXHD1
Fuchs Corneal Dystrophy
Fuchs' Endothelial Dystrophy
Middle Aged
Phenotype
Pedigree
030104 developmental biology
Child
Preschool
030221 ophthalmology & optometry
Female
Carrier Proteins
Rare cancers Radboud Institute for Health Sciences [Radboudumc 9]
Zdroj: Clinical Genetics, 94(2), 221-231. Wiley-Blackwell
Clinical Genetics, 94(2), 221. Wiley-Blackwell
Clinical Genetics, 94, 221-231
Wesdorp, M, Schreur, V, Beynon, A J, Oostrik, J, van de Kamp, J M, Elting, M W, van den Boogaard, M J H, Feenstra, I, Admiraal, R J C, Kunst, H P M, Hoyng, C B, Kremer, H, Yntema, H G, Pennings, R J E & Schraders, M 2018, ' Further audiovestibular characterization of DFNB77, caused by deleterious variants in LOXHD1, and investigation into the involvement of Fuchs corneal dystrophy ', Clinical Genetics, vol. 94, no. 2, pp. 221-231 . https://doi.org/10.1111/cge.13368
Clinical Genetics, 94, 2, pp. 221-231
ISSN: 0009-9163
DOI: 10.1111/cge.13368
Popis: This study focuses on further characterization of the audiovestibular phenotype and on genotype-phenotype correlations of DFNB77, an autosomal recessive type of hearing impairment (HI). DFNB77 is associated with disease-causing variants in LOXHD1, and is genetically and phenotypically highly heterogeneous. Heterozygous deleterious missense variants in LOXHD1 have been associated with late-onset Fuchs corneal dystrophy (FCD). However, up to now screening for FCD of heterozygous carriers in DFNB77 families has not been reported. This study describes the genotype and audiovestibular phenotype of 9 families with DFNB77. In addition, carriers within the families were screened for FCD. Fifteen pathogenic missense and truncating variants were identified, of which 12 were novel. The hearing phenotype showed high inter- and intrafamilial variation in severity and progression. There was no evidence for involvement of the vestibular system. None of the carriers showed (pre-clinical) symptoms of FCD. Our findings expand the genotypic and phenotypic spectrum of DFNB77, but a clear correlation between the type or location of the variant and the severity or progression of HI could not be established. We hypothesize that environmental factors or genetic modifiers are responsible for phenotypic differences. No association was found between heterozygous LOXHD1 variants and the occurrence of FCD in carriers.
Databáze: OpenAIRE
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