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Genetic analysis of SLC26A4 gene (pendrin) related deafness among a cohort of assortative mating families from southern India

  • Otology
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Abstract

Purpose

Assortative mating (AM) or preferential mating is known to influence the genetic architecture of the hearing-impaired (HI) population. AM is now seen as a universal phenomenon with individuals seeking partners based on quantitative, qualitative, and behavioral phenotypes. However, the molecular genetic dynamics of AM among the HI tested in real time are limited to the DFNB1 locus.

Methods

A total of 113 HI partners from 82 South Indian families (52 deaf marrying deaf and 30 deaf marrying normal), previously excluded for DFNB1 (GJB2/6) etiology, were screened for SLC26A4 gene (DFNB4) variants.

Results

A spectrum of seven pathogenic variants viz., p.S90L, p.V239D, p.V359E, p.Gly389Trpfs*79 (novel), p.T410M, p.N457K and p.K715N were identified. The pathogenic allele frequency of SLC26A4 variants identified in this study was 3.98% (9/226).

Conclusion

We recommend a preliminary screening of mutational hotspots for future investigations to rapidly test for its recurrence among South Indian HI population. This will be the first study to comprehensively account for the incidence of SLC26A4 gene variants and the real-time dynamics of DFNB4 variants among this type of a HI cohort.

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Acknowledgements

We wish to record our profound gratitude to Prof. Alan Bittles, Murdoch University, Australia, for the scientific editing of this manuscript. We are grateful to the hearing-impaired families for their cooperation and participation in this study. This study was supported by major research grants from ad hoc research project (5/8/10-17(Oto)/CFP/2011-NCD-I) from the Indian Council of Medical Research (ICMR) and DBT multicentric grant (BT/PR26850/MED/12/808/2017); UGC Research Scientist Scheme (F.8-17(SC)/90(SA-II)), Government of India, sanctioned to CRS. JMJ was supported by CSIR and currently by DBT SRF; NDG by CSIR SRF. We are thankful to Dr. Suriyakumar Govindarajulu, Anderson Diagnostics & Labs, Chennai, for doing radiological investigations for SLC26A4-positive probands.

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Author notes

  1. Amritkumar Pavithra

    Present address: PG and Research Department of Biotechnology, Women’s Christian College, Chennai, India

Authors and Affiliations

  1. Department of Genetics, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai, 600 113, India

    Jayasankaran Chandru, Justin Margret Jeffrey, Amritkumar Pavithra, S. Paridhy Vanniya, G. Nandhini Devi, Subathra Mahalingam & C. R. Srikumari Srisailapathy

  2. Hearing Care Center, Anna Nagar, Chennai, 600 040, India

    Natarajan Padmavathy Karthikeyen

Authors
  1. Jayasankaran Chandru
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  4. S. Paridhy Vanniya
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  5. G. Nandhini Devi
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  8. C. R. Srikumari Srisailapathy
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Contributions

CRS contributed to the conceptualization of this study and obtained funding. CRS, AP, JC, JMJ, and SPV recruited deaf families for the study from four different states, collected detailed clinical data, family history and pedigrees, and isolated DNA from blood samples. AP and JMJ carried out all molecular analysis associated with DFNB1 mutations; JC, SPV, NDG, SM, and JMJ contributed in molecular screening of non-GJB2 gene set. NPK carried out the extended clinical investigations for the SLC26A4-positive families; CRS, JC, and JMJ prepared the original draft and all authors contributed to editing and review and provided intellectual input to the final manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to C. R. Srikumari Srisailapathy.

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Ethics statement

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional human ethical committee—approval no: UM/IHEC/03-2014-II.

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Informed consent was obtained from all individual participants included in the study.

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Chandru, J., Jeffrey, J.M., Pavithra, A. et al. Genetic analysis of SLC26A4 gene (pendrin) related deafness among a cohort of assortative mating families from southern India. Eur Arch Otorhinolaryngol 277, 3021–3035 (2020). https://doi.org/10.1007/s00405-020-06026-3

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