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A novel biallelic single base insertion in WNK1 in a Pakistani family with congenital insensitivity to pain

Journal of Human Genetics volume 65, pages 493–496 (2020)Cite this article

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Abstract

Hereditary sensory and autonomic neuropathy type II (HSANII) is a rare, recessively inherited neurological condition frequently involving insensitivity to pain. The subtype, HSAN2A, results from mutations in the gene WNK1. We identified a consanguineous Pakistani family with three affecteds showing symptoms of HSANII. We performed microarray genotyping, followed by homozygosity-by-descent (HBD) mapping, which indicated several significant HBD regions, including ~6 Mb towards the terminus of chromosome 12p, spanning WNK1. Simultaneously, we performed whole exome sequencing (WES) on one of the affected brothers, and identified a homozygous 1 bp insertion variant, Chr12:978101dupA, within exon 10. This variant, confirmed to segregate in the family, is predicted to truncate the protein (NM_213655.4:c.3464delinsAC; p.(Thr1155Asnfs*11) and lead to nonsense-mediated mRNA decay of the transcript. Previous studies of congenital pain insensitivity/HSANII in Pakistani families have identified mutations in SCN9A. Our study identified a previously unreported WNK1 mutation segregating with congenital pain insensitivity/HSANII in a Pakistani family.

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Fig. 1

Data availability

Information on the variant reported here has been submitted to the ClinVar database housed by NCBI: ClinVar accession SCV001134973. The microarray and WES data that support the findings of this study are available from the corresponding author upon reasonable request.

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Acknowledgements

The authors thank the family for their participation in this study. This study was supported by funding from the Canadian Institutes of Health Research to JBV (#PJT-156402).

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Authors and Affiliations

  1. Molecular Neuropsychiatry & Development (MiND) Lab, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada

    Stephen Pastore, Ricardo Harripaul & John B. Vincent

  2. Institute of Medical Science, University of Toronto, Toronto, ON, Canada

    Stephen Pastore, Ricardo Harripaul & John B. Vincent

  3. Department of Pediatrics and Child Neurology, Wah Medical College, Wah Cantonment, Punjab, Pakistan

    Matloob Azam

  4. Department of Psychiatry, University of Toronto, Toronto, ON, Canada

    John B. Vincent

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  1. Stephen Pastore
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  2. Ricardo Harripaul
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  3. Matloob Azam
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  4. John B. Vincent
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Correspondence to John B. Vincent.

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Pastore, S., Harripaul, R., Azam, M. et al. A novel biallelic single base insertion in WNK1 in a Pakistani family with congenital insensitivity to pain. J Hum Genet 65, 493–496 (2020). https://doi.org/10.1038/s10038-020-0734-x

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  • DOI: https://doi.org/10.1038/s10038-020-0734-x

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