Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • Vascular Malformations (Apr 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact

Citations to this article

Modifier variant of METTL13 suppresses human GAB1–associated profound deafness
Rizwan Yousaf, … , Thomas B. Friedman, Saima Riazuddin
Rizwan Yousaf, … , Thomas B. Friedman, Saima Riazuddin
Published February 6, 2018
Citation Information: J Clin Invest. 2018;128(4):1509-1522. https://doi.org/10.1172/JCI97350.
View: Text | PDF
Research Article Genetics Otology Article has an altmetric score of 1

Modifier variant of METTL13 suppresses human GAB1–associated profound deafness

  • Text
  • PDF
Abstract

A modifier variant can abrogate the risk of a monogenic disorder. DFNM1 is a locus on chromosome 1 encoding a dominant suppressor of human DFNB26 recessive, profound deafness. Here, we report that DFNB26 is associated with a substitution (p.Gly116Glu) in the pleckstrin homology domain of GRB2-associated binding protein 1 (GAB1), an essential scaffold in the MET proto-oncogene, receptor tyrosine kinase/HGF (MET/HGF) pathway. A dominant substitution (p.Arg544Gln) of METTL13, encoding a predicted methyltransferase, is the DFNM1 suppressor of GAB1-associated deafness. In zebrafish, human METTL13 mRNA harboring the modifier allele rescued the GAB1-associated morphant phenotype. In mice, GAB1 and METTL13 colocalized in auditory sensory neurons, and METTL13 coimmunoprecipitated with GAB1 and SPRY2, indicating at least a tripartite complex. Expression of MET-signaling genes in human lymphoblastoid cells of individuals homozygous for p.Gly116Glu GAB1 revealed dysregulation of HGF, MET, SHP2, and SPRY2, all of which have reported variants associated with deafness. However, SPRY2 was not dysregulated in normal-hearing humans homozygous for both the GAB1 DFNB26 deafness variant and the dominant METTL13 deafness suppressor, indicating a plausible mechanism of suppression. Identification of METTL13-based modification of MET signaling offers a potential therapeutic strategy for a wide range of associated hearing disorders. Furthermore, MET signaling is essential for diverse functions in many tissues including the inner ear. Therefore, identification of the modifier of MET signaling is likely to have broad clinical implications.

Authors

Rizwan Yousaf, Zubair M. Ahmed, Arnaud P.J. Giese, Robert J. Morell, Ayala Lagziel, Alain Dabdoub, Edward R. Wilcox, Sheikh Riazuddin, Thomas B. Friedman, Saima Riazuddin

×

Total citations by year

Year: 2024 2023 2022 2021 2020 2019 2018 2009 Total
Citations: 5 1 4 5 5 3 2 1 26
Citation information
This citation data is accumulated from CrossRef, which receives citation information from participating publishers, including this journal. Not all publishers participate in CrossRef, so this information is not comprehensive. Additionally, data may not reflect the most current citations to this article, and the data may differ from citation information available from other sources (for example, Google Scholar, Web of Science, and Scopus).

Citations to this article (26)

Title and authors Publication Year
Autosomal recessive non‐syndromic hearing loss genes in Pakistan during the previous three decades
Shadab M, Abbasi AA, Ejaz A, Ben\u2010Mahmoud A, Gupta V, Kim H, Vona B
Journal of Cellular and Molecular Medicine 2024
Clinical Genetic Testing for Hearing Loss: Implications for Genetic Counseling and Gene-Based Therapies
Lee NK, Uhler KM, Yoon PJ, Santos-Cortez RL
Biomedicines 2024
METTL Family in Healthy and Disease.
He J, Hao F, Song S, Zhang J, Zhou H, Zhang J, Li Y
Molecular biomedicine 2024
Biological Relevance of Dual Lysine and N-Terminal Methyltransferase METTL13
Boulter M, Biggar KK
Biomolecules 2024
Fine mapping of candidate effector genes for heart rate
Ramírez J, van Duijvenboden S, Young WJ, Chen Y, Usman T, Orini M, Lambiase PD, Tinker A, Bell CG, Morris AP, Munroe PB
Human Genetics 2024
Three's a crowd – why did three N-terminal methyltransferases evolve for one job?
Conner MM, Schaner Tooley CE
Journal of cell science 2023
Methods to Improve Molecular Diagnosis in Genomic Cold Cases in Pediatric Neurology
M Kadlubowska, I Schrauwen
Genes & development 2022
ARNSHL gene identification: past, present and future.
Imtiaz A
Molecular genetics and genomics : MGG 2022
Mutation screening of the CYP1B1 gene reveals thirteen novel disease-causing variants in consanguineous Pakistani families causing primary congenital glaucoma
Tehreem R, Arooj A, Siddiqui SN, Naz S, Afshan K, Firasat S
PloS one 2022
New Insights into the Identity of the DFNA58 Gene
do Nascimento LR, Vieira-Silva GA, Kitajima JP, Batissoco AC, Lezirovitz K
Genes & development 2022
Identification of autosomal recessive nonsyndromic hearing impairment genes through the study of consanguineous and non-consanguineous families: past, present, and future
A Acharya, I Schrauwen, SM Leal
Human Genetics 2021
Structure, Activity and Function of the Dual Protein Lysine and Protein N-Terminal Methyltransferase METTL13
ME Jakobsson
Life Sciences 2021
Molecular genetic landscape of hereditary hearing loss in Pakistan
S Naz
Human Genetics 2021
UBA2 variants underlie a recognizable syndrome with variable aplasia cutis congenita and ectrodactyly
RE Schnur, S Yousaf, J Liu, WK Chung, L Rhodes, M Marble, RM Zambrano, N Sobreira, P Jayakar, ME Pierpont, MJ Schultz, PN Pichurin, RJ Olson, GE Graham, M Osmond, GA Contreras-García, KA Campo-Neira, CA Peñaloza-Mantilla, M Flage, S Kuppa, K Navarro, MJ Sacoto, IM Wentzensen, MI Scarano, J Juusola, CE Prada, RB Hufnagel
Genetics in Medicine 2021
SLC22A4 Gene in Hereditary Non-syndromic Hearing Loss: Recurrence and Incomplete Penetrance of the p.C113Y Mutation in Northwest Africa
C Chiereghin, M Robusto, L Mauri, P Primignani, P Castorina, U Ambrosetti, S Duga, R Asselta, G Soldà
Frontiers in Genetics 2021
Small fish, big prospects: using zebrafish to unravel the mechanisms of hereditary hearing loss
B Vona, J Doll, MA Hofrichter, T Haaf, GK Varshney
Hearing Research 2020
The GENDULF algorithm: mining transcriptomics to uncover modifier genes for monogenic diseases
N Auslander, DM Ramos, I Zelaya, H Karathia, TO Crawford, AA Schäffer, CJ Sumner, E Ruppin
Molecular Systems Biology 2020
Metformin reduces HGF-induced resistance to alectinib via the inhibition of Gab1
H Chen, C Lin, T Peng, C Hu, C Lu, L Li, Y Wang, R Han, M Feng, FF Sun, Y He
Cell Death and Disease 2020
Mouse Models of Human Pathogenic Variants of TBC1D24 Associated with Non-Syndromic Deafness DFNB86 and DFNA65 and Syndromes Involving Deafness
R Tona, IA Lopez, C Fenollar-Ferrer, R Faridi, C Anselmi, AA Khan, M Shahzad, RJ Morell, S Gu, M Hoa, L Dong, A Ishiyama, IA Belyantseva, S Riazuddin, TB Friedman
Genes & development 2020
A rare genomic duplication in 2p14 underlies autosomal dominant hearing loss DFNA58
K Lezirovitz, GA Vieira-Silva, AC Batissoco, D Levy, JP Kitajima, A Trouillet, E Ouyang, N Zebarjadi, J Sampaio-Silva, V Pedroso-Campos, LR Nascimento, CY Sonoda, VM Borges, LG Vasconcelos, RM Beck, SS Grasel, DJ Jagger, N Grillet, RF Bento, RC Mingroni-Netto, J Oiticica
Human Molecular Genetics 2020
Growth factor and receptor malfunctions associated with human genetic deafness
S Naz, TB Friedman
Clinical Genetics 2019
The phenotypic landscape of a Tbc1d24 mutant mouse includes convulsive seizures resembling human early infantile epileptic encephalopathy
R Tona, W Chen, Y Nakano, LD Reyes, RS Petralia, YX Wang, MF Starost, TT Wafa, RJ Morell, KD Cravedi, J du Hoffmann, T Miyoshi, JP Munasinghe, TS Fitzgerald, Y Chudasama, K Omori, C Pierpaoli, B Banfi, L Dong, IA Belyantseva, TB Friedman
Human Molecular Genetics 2019
Bi-allelic Variants in METTL5 Cause Autosomal-Recessive Intellectual Disability and Microcephaly
EM Richard, DL Polla, MZ Assir, M Contreras, M Shahzad, AA Khan, A Razzaq, J Akram, MN Tarar, TA Blanpied, ZM Ahmed, RA Jamra, D Wieczorek, H van Bokhoven, S Riazuddin, S Riazuddin
The American Journal of Human Genetics 2019
Genetic Hearing Loss and Gene Therapy
NT Carpena, MY Lee
Genomics & Informatics 2018
FAM92A Underlies Nonsyndromic Postaxial Polydactyly in Humans and an Abnormal Limb and Digit Skeletal Phenotype in Mice: FAM92A UNDERLIES NONSYNDROMIC POSTAXIAL POLYDACTYLY
I Schrauwen, AP Giese, A Aziz, DT Lafont, I Chakchouk, RL Santos-Cortez, K Lee, A Acharya, FS Khan, A Ullah, DA Nickerson, MJ Bamshad, G Ali, S Riazuddin, M Ansar, W Ahmad, ZM Ahmed, SM Leal
Journal of Bone and Mineral Research 2018
Pulmonary surfactant: an immunological perspective
ZC Chroneos, Z Sever-Chroneos, VL Shepherd
Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 2009

← Previous 1 2 Next →

Advertisement

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts

Posted by 2 X users
38 readers on Mendeley
See more details