{"entity": "researcher", "timestamp": "2026-08-29T04:23:13.555Z", "family": "Santos-Cortez", "given": "Regie Lyn P", "initials": "RLP", "orcid": "0000-0002-9958-2535", "affiliations": ["Department of Otolaryngology-Head and Neck Surgery, School of Medicine, University of Colorado Anschutz Medical Campus (CU-AMC), 12700 E. 19th Ave, Aurora, CO, 80045, USA. regie.santos-cortez@cuanschutz.edu.", "Center for Children's Surgery, CHCO, 13123 E. 16th Ave, Aurora, CO, 80045, USA. regie.santos-cortez@cuanschutz.edu."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/dd914a627bf34645b031e77b6aa5a80d.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/dd914a627bf34645b031e77b6aa5a80d"}}, "publications": [{"entity": "publication", "iuid": "908d023f725444c5b72f5d600ead68ac", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/908d023f725444c5b72f5d600ead68ac.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/908d023f725444c5b72f5d600ead68ac"}}, "title": "Rare and low-frequency variants in families with otitis media.", "authors": [{"family": "Santos-Cortez", "given": "Regie Lyn P", "initials": "RLP", "orcid": "0000-0002-9958-2535", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/dd914a627bf34645b031e77b6aa5a80d.json"}}, {"family": "Elling", "given": "Christina L", "initials": "CL"}, {"family": "Gomez", "given": "Helen Z", "initials": "HZ"}, {"family": "Einarsdottir", "given": "Elisabet", "initials": "E"}, {"family": "Kere", "given": "Juha", "initials": "J"}, {"family": "Mattila", "given": "Petri S", "initials": "PS"}, {"family": "Hafr\u00e9n", "given": "Lena", "initials": "L"}, {"family": "Ryan", "given": "Allen F", "initials": "AF"}], "type": "journal article", "published": "2025-05-00", "journal": {"title": "J. Mol. Med.", "issn": "1432-1440", "volume": "103", "issue": "5", "pages": "559-570", "issn-l": "0946-2716"}, "abstract": "Otitis media is a highly frequent diagnosis in children that causes significant morbidity but remains understudied as a genetic trait despite significant heritability in families. To identify rare or low-frequency variants within genes that confer susceptibility to otitis media, exome sequence data of 287 individuals from 243 families were analyzed. Identified variants were tested for co-segregation with otitis media in family members. Genome sequence data from a case-control cohort was imputed and analyzed for association of specific genes with otitis media. Single-cell RNA-sequence data of identified genes were noted in acutely infected mouse middle ears. Thirty-three variants within 24 genes co-segregated with otitis media in 28 families, of which 18 variants were considered pathogenic or likely pathogenic. An additional 81 variants in 21 of the same genes were identified in 83 unrelated probands with otitis media. Of the 24 genes, 12 were associated with otitis media in mouse models, while 15 genes were replicated from previous human studies. A common variant EYA4 c.829G > A was associated with OM in the case-control cohort. Using network analysis, 22 of the 24 genes were connected in a subnetwork enriched in various signaling pathways, Th1/Th2/Th17 cell differentiation, and viral infections. Majority (87.5%) of the identified genes were expressed in mouse middle ear cells, with differential expression after acute infection. The identification of novel genes and variants for susceptibility to otitis media will be useful in future risk screening and clinical management in children that require a more personalized approach due to poor response to standard treatments. KEY MESSAGES: Thirty-three variants in 24 genes were identified in 28 families with otitis media. Eighteen of these variants within 10 genes were considered (likely) pathogenic. A common variant EYA4 c.829G > A was associated with OM in a case-control cohort. The novel genes were differentially expressed in mouse middle ear post-infection. Genetic screening could identify children for targeted treatment for otitis media.", "doi": "10.1007/s00109-025-02537-w", "pmid": "40183840", "labels": [], "xrefs": [{"db": "pii", "key": "10.1007/s00109-025-02537-w"}], "notes": [], "created": "2026-08-21T11:05:27.710Z", "modified": "2026-08-21T11:05:27.769Z"}, {"entity": "publication", "iuid": "3527bd51cae545bb858c02ebf90143d9", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/3527bd51cae545bb858c02ebf90143d9.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/3527bd51cae545bb858c02ebf90143d9"}}, "title": "The role of CDHR3 in susceptibility to otitis media.", "authors": [{"family": "Hirsch", "given": "Scott D", "initials": "SD"}, {"family": "Elling", "given": "Christina L", "initials": "CL"}, {"family": "Bootpetch", "given": "Tori C", "initials": "TC"}, {"family": "Scholes", "given": "Melissa A", "initials": "MA"}, {"family": "Hafr\u00e9n", "given": "Lena", "initials": "L"}, {"family": "Streubel", "given": "Sven-Olrik", "initials": "SO"}, {"family": "Pine", "given": "Harold S", "initials": "HS"}, {"family": "Wine", "given": "Todd M", "initials": "TM"}, {"family": "Szeremeta", "given": "Wasyl", "initials": "W"}, {"family": "Prager", "given": "Jeremy D", "initials": "JD"}, {"family": "Einarsdottir", "given": "Elisabet", "initials": "E"}, {"family": "Yousaf", "given": "Ayesha", "initials": "A"}, {"family": "Baschal", "given": "Erin E", "initials": "EE"}, {"family": "Rehman", "given": "Sakina", "initials": "S"}, {"family": "Bamshad", "given": "Michael J", "initials": "MJ"}, {"family": "Nickerson", "given": "Deborah A", "initials": "DA"}, {"family": "Riazuddin", "given": "Saima", "initials": "S"}, {"family": "Leal", "given": "Suzanne M", "initials": "SM"}, {"family": "Ahmed", "given": "Zubair M", "initials": "ZM"}, {"family": "Yoon", "given": "Patricia J", "initials": "PJ"}, {"family": "Kere", "given": "Juha", "initials": "J"}, {"family": "Chan", "given": "Kenny H", "initials": "KH"}, {"family": "Mattila", "given": "Petri S", "initials": "PS"}, {"family": "Friedman", "given": "Norman R", "initials": "NR"}, {"family": "Chonmaitree", "given": "Tasnee", "initials": "T"}, {"family": "Frank", "given": "Daniel N", "initials": "DN"}, {"family": "Ryan", "given": "Allen F", "initials": "AF"}, {"family": "Santos-Cortez", "given": "Regie Lyn P", "initials": "RLP", "orcid": "0000-0002-9958-2535", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/dd914a627bf34645b031e77b6aa5a80d.json"}}], "type": "journal article", "published": "2021-11-00", "journal": {"title": "J. Mol. Med.", "issn": "1432-1440", "volume": "99", "issue": "11", "pages": "1571-1583", "issn-l": "0946-2716"}, "abstract": "Otitis media (OM) is common in young children and can cause hearing loss and speech, language, and developmental delays. OM has high heritability; however, little is known about OM-related molecular and genetic processes. CDHR3 was previously identified as a locus for OM susceptibility, but to date, studies have focused on how the CDHR3 p.Cys529Tyr variant increases epithelial binding of rhinovirus-C and risk for lung or sinus pathology. In order to further delineate a role for CDHR3 in OM, we performed the following: exome sequencing using DNA samples from OM-affected individuals from 257 multi-ethnic families; Sanger sequencing, logistic regression and transmission disequilibrium tests for 407 US trios or probands with OM; 16S rRNA sequencing and analysis for middle ear and nasopharyngeal samples; and single-cell RNA sequencing and differential expression analyses for mouse middle ear. From exome sequence data, we identified a novel pathogenic CDHR3 splice variant that co-segregates with OM in US and Finnish families. Additionally, a frameshift and six missense rare or low-frequency variants were identified in Finnish probands. In US probands, the CDHR3 p.Cys529Tyr variant was associated with the absence of middle ear fluid at surgery and also with increased relative abundance of Lysobacter in the nasopharynx and Streptomyces in the middle ear. Consistent with published data on airway epithelial cells and our RNA-sequence data from human middle ear tissues, Cdhr3 expression is restricted to ciliated epithelial cells of the middle ear and is downregulated after acute OM. Overall, these findings suggest a critical role for CDHR3 in OM susceptibility. KEY MESSAGES: \u2022 Novel rare or low-frequency CDHR3 variants putatively confer risk for otitis media. \u2022 Pathogenic variant CDHR3 c.1653 + 3G > A was found in nine families with otitis media. \u2022 CDHR3 p.Cys529Tyr was associated with lack of effusion and bacterial otopathogens. \u2022 Cdhr3 expression was limited to ciliated epithelial cells in mouse middle ear. \u2022 Cdhr3 was downregulated 3 h after infection of mouse middle ear.", "doi": "10.1007/s00109-021-02118-7", "pmid": "34322716", "labels": [], "xrefs": [{"db": "mid", "key": "NIHMS1731147"}, {"db": "pmc", "key": "PMC8541908"}, {"db": "pii", "key": "10.1007/s00109-021-02118-7"}], "notes": [], "created": "2026-08-21T11:05:25.507Z", "modified": "2026-08-21T11:05:25.596Z"}]}