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Exclusion of Putative CATSPER2 and STRC Gene Deletion and FOXI1 Gene Mutations in a Unique Cohort with Sensorineural Deafness and Male Infertility from South India


Affiliations
1 Department of Genetics, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai 600 113, India
2 Post Graduate and Research Department of Biotechnology, Women’s Christian College, College Road, Chennai 600 006, India
3 Department of Medical Genetics, Apollo Hospitals, Chennai 600 006, India
 

Prelingual genetic deafness and male infertility can appear as isolated findings or as part of a syndrome. Deafness-Infertility Syndrome (DIS) was previously reported to be caused due to a rare contiguous gene deletion of CATSPER2 and STRC genes on chromosome 15q15.3. We tested this contiguous gene deletion in a unique cohort of 15 probands with deafness and male infertility, who were partners in assortative mating from south India. Screening for this alleged contiguous gene deletion did not test positive. Given high parental consanguinity, it is possible that infertility and deafness may not be part of a contiguous gene deletion, but two independent events. As a next option we screened another candidate gene FOXI1 (5q35.1), known to independently influence sperm maturation and also encode transcriptional factor of a deafness gene SLC26A4, to implicate for this DIS phenotype. However none of the probands had any pathogenic mutations in FOXI1 gene. Having excluded (i) DIS contiguous gene deletion and (ii) FOXI1 gene mutations’ role in this phenotype, we conclude that this unique cohort’s genetic etiology can be resolved using high-throughput NGS and CNV assessment. This approach may also identify potential linkage to any novel genes.

Keywords

Assortative Mating, Contiguous Gene Deletion, CATSPER2, STRC, p.I35S.
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  • Hoppmann, N., Aypar, U., Brodersen, P., Brown, N., Wilson, J. and Babovic-Vuksanovic, D., Genetic testing for hearing loss in the United States should include deletion/duplication analysis for the deafness/infertility locus at 15q15. 3. Mol. Cytogenet., 2013, 6, 1.

  • Quill, T. A., Ren, D., Clapham, D. E. and Garbers, D. L., A voltagegated ion channel expressed specifically in spermatozoa. Proc. Natl. Acad. Sci. USA, 2001, 98, 12527–12531.

  • Quill, T. A., Sugden, S. A., Rossi, K. L., Doolittle, L. K., Hammer, R. E. and Garbers, D. L., Hyperactivated sperm motility driven by CatSper2 is required for fertilization. Proc. Natl. Acad. Sci. USA, 2003, 100, 14869–14874.

  • Francey, L. J. et al., Genome-wide SNP genotyping identifies the Stereocilin (STRC) gene as a major contributor to pediatric bilateral sensorineural hearing impairment. Am. J. Med. Genet. Part A, 2012, 158, 298–308.

  • Hildebrand, M. S., Avenarius, M. R. and Smith, R. J., CATSPER-related male infertility; http://www.ncbi.nlm.nih.gov/books/NBK22925

  • Yang, T., Vidarsson, H., Rodrigo-Blomqvist, S., Rosengren, S. S., Enerbäck, S. and Smith, R. J., Transcriptional control of SLC26A4 is involved in Pendred syndrome and nonsyndromic enlargement of vestibular aqueduct (DFNB4). Am. J. Human Genet., 2007, 80, 1055–1063.

  • Blomqvist, S. R., Vidarsson, H., Söder, O. and Enerbäck, S., Epididymal expression of the forkhead transcription factor Foxi1 is required for male fertility. EMBO J., 2006, 25, 4131–4141.

  • Sambrook, J. F. and Russell, D. W., Molecular cloning: A Laboratory Manual, Cold Spring Harbor Laboratory Press, 2001, 3rd edn, pp. 2100.

  • Denise, E. R.. Human Cytogenetics: Constitutional Analysis – A practical Approach, Oxford University Press, 2000, pp. 33–54.

  • McGowan-Jordan, J., Simons, A. and Schmid, M. (eds). An International System for Human Cytogenomic Nomenclature. Reprint of: cytogenetic and Genome Research, Karger. Medical and Scientific Publishers, 2016, p. 149.

  • Zhang, Y. et al., Sensorineural deafness and male infertility: a contiguous gene deletion syndrome. J. Med. Genet., 2007, 44, 233–240.

  • Cartegni, L., Chew, S. L. and Krainer, A. R., Listening to silence and understanding nonsense: exonic mutations that affect splicing. Nat. Rev. Genet., 2002, 3, 285–298.

  • Sauna, Z. E., and Kimchi-Sarfaty, C., Understanding the contribution of synonymous mutations to human disease. Nat. Rev. Genet., 2011, 12, 683–291.

  • Pritchard, D. J. and Korf, B. R., Medical Genetics at a Glance, Wiley Blackwell John Wiley & Sons Ltd Publication, 2013, 3rd edn, p. 103.

  • Knijnenburg, J. et al., A homozygous deletion of a normal variation locus in a patient with hearing loss from non-consanguineous parents. J. Med. Genet., 2009, 46, 412–417.

  • Avidan, N. et al., CATSPER2, a human autosomal nonsyndromic male infertility gene. Eur. J. Hum. Genet., 2003, 11, 497–502.

  • Jaiswal, D., Singh, V., Dwivedi, U. S., Trivedi, S. and Singh, K., Chromosome microarray analysis: a case report of infertile brothers with CATSPER gene deletion. Gene, 2014, 542, 263–265.

  • Vona, B. et al., Targeted next-generation sequencing of deafness genes in hearing-impaired individuals uncovers informative mutations. Genet. Med., 2014, 16, 945–953.

  • Shearer, A. E. et al., Copy number variants are a common cause of non-syndromic hearing loss. Genome Med., 2014, 6, 37.

  • Gu, X., Guo, L., Ji, H., Sun, S., Chai, R., Wang, L. and Li, H., Genetic testing for sporadic hearing loss using targeted massively parallel sequencing identifies 10 novel mutations. Clin. Geneti., 2015, 87, 588–893.

  • Moteki, H. et al., Detection and confirmation of deafness-causing copy number variations in the STRC gene by massively parallel sequencing and comparative genomic hybridization. Ann. Otol., Rhinol. Laryn., 2016, 125, 918–923.

  • Jeffrey, J. M., Amrutha, K., Charles, S., Chandra, R. S. and Srikumari Srisailapathy, C. R., Screening for contiguous gene deletion in chromosome 15q15.3 among infertile males from Chennai – a pilot study. Proc. Natl. Symp. Genet. in Clin. Med., 2017, 31–34; ISBN: 978-93-5288-254-0.

  • RamShankar, M. et al., Contribution of connexin 26 (GJB2) mutations and founder effect to non-syndromic hearing loss in India. J. Med. Genet., 2003, 40, e68.


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  • Exclusion of Putative CATSPER2 and STRC Gene Deletion and FOXI1 Gene Mutations in a Unique Cohort with Sensorineural Deafness and Male Infertility from South India

Abstract Views: 368  |  PDF Views: 149

Authors

Justin Margret Jeffrey
Department of Genetics, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai 600 113, India
Jayasankaran Chandru
Department of Genetics, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai 600 113, India
Amritkumar Pavithra
Post Graduate and Research Department of Biotechnology, Women’s Christian College, College Road, Chennai 600 006, India
Murugesan Kalaimathi
Department of Genetics, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai 600 113, India
Nagarathinam Indhumathi
Department of Medical Genetics, Apollo Hospitals, Chennai 600 006, India
Pangadan Ashraf
Department of Genetics, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai 600 113, India
C. R. Srikumari Srisailapathy
Department of Genetics, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai 600 113, India

Abstract


Prelingual genetic deafness and male infertility can appear as isolated findings or as part of a syndrome. Deafness-Infertility Syndrome (DIS) was previously reported to be caused due to a rare contiguous gene deletion of CATSPER2 and STRC genes on chromosome 15q15.3. We tested this contiguous gene deletion in a unique cohort of 15 probands with deafness and male infertility, who were partners in assortative mating from south India. Screening for this alleged contiguous gene deletion did not test positive. Given high parental consanguinity, it is possible that infertility and deafness may not be part of a contiguous gene deletion, but two independent events. As a next option we screened another candidate gene FOXI1 (5q35.1), known to independently influence sperm maturation and also encode transcriptional factor of a deafness gene SLC26A4, to implicate for this DIS phenotype. However none of the probands had any pathogenic mutations in FOXI1 gene. Having excluded (i) DIS contiguous gene deletion and (ii) FOXI1 gene mutations’ role in this phenotype, we conclude that this unique cohort’s genetic etiology can be resolved using high-throughput NGS and CNV assessment. This approach may also identify potential linkage to any novel genes.

Keywords


Assortative Mating, Contiguous Gene Deletion, CATSPER2, STRC, p.I35S.

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DOI: https://doi.org/10.18520/cs%2Fv114%2Fi12%2F2538-2542