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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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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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