Update on CD164 and LMX1A genes to strengthen their causative role in autosomal dominant hearing loss

• Published in: Human genetics Vol. 141; no. 3-4; pp. 445 - 453
• Main Authors: Oziębło, Dominika, Lee, Sang‐Yeon, Leja, Marcin Ludwik, Sarosiak, Anna, Bałdyga, Natalia, Skarżyński, Henryk, Kim, Yehree, Han, Jin Hee, Yoo, Hyo Soon, Park, Min Hyun, Choi, Byung Yoon, Ołdak, Monika
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-04-2022; Springer; Springer Nature B.V
• Subjects: Arthrogryposis; Biomedical and Life Sciences; Biomedicine; Deafness - genetics; DNA sequencing; Endolyn - genetics; Family; Gene Function; Genes; Genes, Dominant; Haploinsufficiency; Hearing loss; Hearing Loss - genetics; Hearing Loss, Sensorineural - genetics; Hearing Loss, Sensorineural - pathology; Human Genetics; Humans; LIM-Homeodomain Proteins - genetics; Medical colleges; Metabolic Diseases; Molecular Medicine; Mutation; Nucleotide sequencing; Original Investigation; Pedigree; The Molecular Genetics of Hearing and Deafness; Transcription; Transcription Factors - genetics
• ISSN: 0340-6717; 1432-1203
• DOI: 10.1007/s00439-022-02443-y

Novel hearing loss (HL) genes are constantly being discovered, and evidence from independent studies is essential to strengthen their position as causes of hereditary HL. To address this issue, we searched our genetic data of families with autosomal dominant HL (ADHL) who had been tested with high-throughput DNA sequencing methods. For
CD164
, only one pathogenic variant in one family has so far been reported. For
LMX1A
, just two previous studies have revealed its involvement in ADHL. In this study we found two families with the same pathogenic variant in
CD164
and one family with a novel variant in
LMX1A
(c.686C>A; p.(Ala229Asp)) that impairs its transcriptional activity. Our data show recurrence of the same
CD164
variant in two HL families of different geographic origin, which strongly suggests it is a mutational hotspot. We also provide further evidence for haploinsufficiency as the pathogenic mechanism underlying
LMX1A
-related ADHL.