TY - JOUR T1 - Rising of <em>LOXHD1</em> as a signature causative gene of down-sloping hearing loss in people in their teens and 20s JF - Journal of Medical Genetics JO - J Med Genet SP - 470 LP - 480 DO - 10.1136/jmedgenet-2020-107594 VL - 59 IS - 5 AU - Bong Jik Kim AU - Hyoung Won Jeon AU - Woosung Jeon AU - Jin Hee Han AU - Jayoung Oh AU - Nayoung Yi AU - Min Young Kim AU - Minah Kim AU - Justin Namju Kim AU - Bo Hye Kim AU - Joon Young Hyon AU - Dongsup Kim AU - Ja-Won Koo AU - Doo-Yi Oh AU - Byung Yoon Choi Y1 - 2022/05/01 UR - http://jmg.bmj.com/content/59/5/470.abstract N2 - Background Down-sloping sensorineural hearing loss (SNHL) in people in their teens and 20s hampers efficient learning and communication and in-depth social interactions. Nonetheless, its aetiology remains largely unclear, with the exception of some potential causative genes, none of which stands out especially in people in their teens and 20s. Here, we examined the role and genotype–phenotype correlation of lipoxygenase homology domain 1 (LOXHD1) in down-sloping SNHL through a cohort study.Methods Based on the Seoul National University Bundang Hospital (SNUBH) genetic deafness cohort, in which the patients show varying degrees of deafness and different onset ages (n=1055), we have established the ‘SNUBH Teenager–Young Adult Down-sloping SNHL’ cohort (10–35 years old) (n=47), all of whom underwent exome sequencing. Three-dimensional molecular modelling, minigene splicing assay and short tandem repeat marker genotyping were performed, and medical records were reviewed.Results LOXHD1 accounted for 33.3% of all genetically diagnosed cases of down-sloping SNHL (n=18) and 12.8% of cases in the whole down-sloping SNHL cohort (n=47) of young adults. We identified a potential common founder allele, as well as an interesting genotype–phenotype correlation. We also showed that transcript 6 is necessary and probably sufficient for normal hearing.Conclusions LOXHD1 exceeds other genes in its contribution to down-sloping SNHL in young adults, rising as a signature causative gene, and shows a potential but interesting genotype–phenotype correlation.All data relevant to the study are included in the article or uploaded as supplementary information. The authors confirm that the data supporting the findings of this study are available within the article and its supplementary materials. ER -