Further evidence of involvement of TMEM132E in autosomal recessive nonsyndromic hearing impairment

Journal of Human Genetics volume 65, pages187–192(2020)Cite this article

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Abstract

Autosomal-recessive (AR) nonsyndromic hearing impairment (NSHI) displays a high degree of genetic heterogeneity with >100 genes identified. Recently, TMEM132E, which is highly expressed in inner hair cells, was suggested as a novel ARNSHI gene for DFNB99. A missense variant c.1259G>A: p.(Arg420Gln) in TMEM132E was identified that segregated with ARNSHI in a single Chinese family with two affected members. In the present study, a family of Pakistani origin with prelingual profound sensorineural hearing impairment displaying AR mode of inheritance was investigated via exome and Sanger sequencing. Compound heterozygous variants c.382G>T: p.(Ala128Ser) and c.2204C>T: p.(Pro735Leu) in TMEM132E were observed in affected but not in unaffected family members. TMEM132E variants identified in this and the previously reported ARNSHI family are located in the extracellular domain. In conclusion, we present a second ARNSHI family with TMEM132E variants which strengthens the evidence of the involvement of this gene in the etiology of ARNSHI.

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Acknowledgements

We thank the family members for participating in this study. This work was supported by the Higher Education Commission of Pakistan (to WA) and National Institutes of Health (NIH)-National Institute of Deafness and other Disorders grants R01 DC011651 and R01 DC003594 (to SML).

Funding

This work was supported by the Higher Education Commission of Pakistan (to WA) and National Institutes of Health (NIH)-National Institute of Deafness and other Communication Disorders grants R01 DC011651 and R01 DC003594 (to SML).

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Affiliations

  1. Department of Biotechnology, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan

    Khurram Liaqat, Shabir Hussain & Shoaib Nawaz

  2. Center of Statistical Genetics, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA

    Khurram Liaqat, Shabir Hussain, Anushree Acharya, Isabelle Schrauwen & Suzanne M. Leal

  3. Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan

    Muhammad Bilal, Raja Hussain Ali & Wasim Ahmad

  4. Department of Molecular Science and Technology, Ajou University, Suwon, 443-749, South Korea

    Abdul Nasir

  5. Center for Statistical Genetics, Gertrude H. Sergievsky Center, Taub Institute for Alzheimer’s Disease and the Aging Brain, Department of Neurology, Columbia University Medical Center, 630 W 168th St, New York, NY, 10032, USA

    Anushree Acharya, Isabelle Schrauwen & Suzanne M. Leal

  6. Division of Hematology/Oncology, Boston Children’s Hospital, Boston, MA, 02115, USA

    Raja Hussain Ali

  7. Medical Genomics Research Department, King Abdullah International Medical Research Center (KAIMRC), King Saud bin Abdulaziz University for Health Science, Ministry of National Guard-Health Affairs (MNGHA), P.O. Box 3660, Riyadh, 11481, Saudi Arabia

    Muhammad Umair

Authors
  1. Khurram Liaqat
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  2. Shabir Hussain
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  3. Muhammad Bilal
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  4. Abdul Nasir
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  5. Anushree Acharya
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  6. Raja Hussain Ali
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  7. Shoaib Nawaz
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  8. Muhammad Umair
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  9. Isabelle Schrauwen
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  10. Wasim Ahmad
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  11. Suzanne M. Leal
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Contributions

KL drafted the manuscript and performed data analysis. KL, SH, and IS performed data analysis. KL and AA performed the laboratory experiments. MB, RHA, MU, and SN collected the samples and analyzed the clinical data while protein modeling was performed by AN. WA, IS, and SML edited the manuscript and all authors revised and approved the final manuscript. Funds for the work were obtained by SML.

Corresponding author

Correspondence to Suzanne M. Leal.

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The authors declare that they have no conflict of interest.

Ethical statement

Members of the DEM4877 family provided written informed consents for the proposed study.

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Liaqat, K., Hussain, S., Bilal, M. et al. Further evidence of involvement of TMEM132E in autosomal recessive nonsyndromic hearing impairment. J Hum Genet 65, 187–192 (2020). https://doi.org/10.1038/s10038-019-0691-4

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