Abstract
Mutations in the CEACAM6 gene were first described as causing autosomal dominant nonsyndromic hearing loss, but two splice-altering variants have been recently described as causing autosomal recessive nonsyndromic hearing loss. We describe the novel and extremely rare loss-of-function variant c.436 C > T/p.(Arg146Ter) in the CEACAM16 gene segregating with post-lingual progressive autosomal recessive hearing loss. This variant is predicted to significantly reduce the size of the wild type protein. Our results give additional support that loss-of-function variants in CEACAM16 cause autosomal recessive hearing loss in humans.
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
Shearer AE, Hildebrand MS, Smith RJH. Hereditary Hearing Loss and Deafness Overview. 1999 Feb 14 [Updated 2017 Jul 27]. (eds.Adam MP, Ardinger HH, Pagon RA, et al.) (GeneReviews® [Internet]. Seattle, WA: University of Washington, Seattle; 1993–2018).
Goodyear RJ, Richardson GP. Structure, function, and development of the tectorial membrane: an extracellular matrix essential for hearing. In: Current Topics in Developmental Biology. Academic Press; 2018. p. 217–44.
Cheatham MA, Ahmad A, Zhou Y, Goodyear RJ, Dallos P, Richardson GP. Increased spontaneous otoacoustic emissions in mice with a detached tectorial membrane. J Assoc Res Otolaryngol. 2016;17:81–88.
Kuespert K, Pils S, Hauck CR. CEACAMs: their role in physiology and pathophysiology. Curr Opin Cell Biol. 2006;18:565–71.
Richardson GP, Lukashkin AN, Russell IJ. The tectorial membrane: one slice of a complex cochlear sandwich. Curr Opin Otolaryngol Head Neck Surg. 2008;16:458–64.
Hildebrand MS, Morín M, Meyer NC, Mayo F, Modamio-Hoybjor S, Mencía A, et al. DFNA8/12 caused by TECTA mutations is the most identified subtype of nonsyndromic autosomal dominant hearing loss. Hum Mutat. 2011;32:825–34.
Donaudy F, Snoeckx R, Pfister M, Zenner HP, Blin N, Di Stazio M, et al. Nonmuscle myosin heavy-chain gene MYH14 is expressed in cochlea and mutated in patients affected by autosomal dominant hearing impairment (DFNA4). Am J Hum Genet. 2004;74:770–6.
Wang H, Wang X, He C, Li H, Qing J, Grati M, et al. Exome sequencing identifies a novel CEACAM16 mutation associated with autosomal dominant nonsyndromic hearing loss DFNA4B in a Chinese family. J Hum Genet. 2015;60:119–26.
Hofrichter MAH, Nanda I, Gräf J, Schröder J, Shehata-Dieler W, Vona B, et al. A novel de novo mutation in CEACAM16 associated with postlingual hearing impairment. Mol Syndromol. 2015;6:156–63.
Zheng J, Miller KK, Yang T, Hildebrand MS, Shearer AE, DeLuca AP, et al. Carcinoembryonic antigen-related cell adhesion molecule 16 interacts with -tectorin and is mutated in autosomal dominant hearing loss (DFNA4). Proc Natl Acad Sci USA. 2011;108:4218–23.
Kammerer R, Rüttiger L, Riesenberg R, Schäuble C, Krupar R, Kamp, A, et al. Loss of mammal-specific tectorial membrane component carcinoembryonic antigen cell adhesion molecule 16 (CEACAM16) leads to hearing impairment at low and high frequencies. J Biol Chem. 2012;287:21584–98.
Lezirovitz K, Nicastro FS, Pardono E, Abreu-Silva RS, Batissoco AC, Neustein I, et al. Is autosomal recessive deafness associated with oculocutaneous albinism a “coincidence syndrome”?. J Hum Genet. 2006; https://doi.org/10.1007/s10038-006-0003-7.
Caires-Júnior LC, Goulart E, Melo US, Araujo B, Alvizi L, Soares-Schanoski A, et al. Discordant congenital Zika syndrome twins show differential in vitro viral susceptibility of neural progenitor cells. Nat Commun. 2018;9:475.
Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17:405–24.
Booth KT, Kahrizi K, Najmabadi H, Azaiez H, Smith RJ. Old gene, new phenotype: splice-altering variants in CEACAM16 cause recessive non-syndromic hearing impairment. J Med Genet. 2018. https://doi.org/10.1136/jmedgenet-2018-105349.
Acknowledgements
The authors are indebted to Humberto Cezar Marcolino for technical assistance. We thank Dr. Alfredo Tabith Junior and all DERDIC staff for clinical assistance. This work was supported by FAPESP - CEPID Human Genome Research Center 2013/08028-1, Coordinator: Mayana Zatz). We thank all family members for participation in the study.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Rights and permissions
About this article
Cite this article
Dias, A.M.M., Lezirovitz, K., Nicastro, F.S. et al. Further evidence for loss-of-function mutations in the CEACAM16 gene causing nonsyndromic autosomal recessive hearing loss in humans. J Hum Genet 64, 257–260 (2019). https://doi.org/10.1038/s10038-018-0546-4
Received:
Revised:
Accepted:
Published:
Issue date:
DOI: https://doi.org/10.1038/s10038-018-0546-4
This article is cited by
-
Frequency and origin of the c.2090T>G p.(Leu697Trp) MYO3A variant associated with autosomal dominant hearing loss
European Journal of Human Genetics (2022)
-
Genetic etiology of non-syndromic hearing loss in Latin America
Human Genetics (2022)
