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Please use this identifier to cite or link to this item: http://repository.li.mahidol.ac.th/dspace/handle/123456789/47483
Title: Loss-of-function mutations of SCN10A encoding Na <inf>V</inf> 1.8 α subunit of voltage-gated sodium channel in patients with human kidney stone disease
Authors: Choochai Nettuwakul
Oranud Praditsap
Nunghathai Sawasdee
Nanyawan Rungroj
Katesirin Ruamyod
Wattana B. Watanapa
Mutita Junking
Sittideth Sangnual
Suchai Sritippayawan
Boonyarit Cheunsuchon
Duangporn Chuawattana
Santi Rojsatapong
Wipada Chaowagul
Sulayman D. Dib-Hajj
Stephen G. Waxman
Pa Thai Yenchitsomanus
Sappasitthiprasong Hospital
Yale University School of Medicine
Faculty of Medicine, Siriraj Hospital, Mahidol University
Keywords: Multidisciplinary
Issue Date: 1-Dec-2018
Citation: Scientific Reports. Vol.8, No.1 (2018)
Abstract: © 2018 The Author(s). Human kidney stone disease (KSD) causes significant morbidity and public health burden worldwide. The etiology of KSD is heterogeneous, ranging from monogenic defects to complex interaction between genetic and environmental factors. However, the genetic defects causing KSD in the majority of affected families are still unknown. Here, we report the discovery of mutations of SCN10A, encoding Na V 1.8 α subunit of voltage-gated sodium channel, in families with KSD. The region on chromosome 3 where SCN10A locates was initially identified in a large family with KSD by genome-wide linkage analysis and exome sequencing. Two mutations (p.N909K and p.K1809R) in the same allele of SCN10A co-segregated with KSD in the affected family. Additional mutation (p.V1149M) of SCN10A was identified in another affected family, strongly supporting the causal role of SCN10A for KSD. The amino acids at these three positions, N909, K1809, and V1149, are highly conserved in vertebrate evolution, indicating their structural and functional significances. Na V 1.8 α subunit mRNA and protein were found to express in human kidney tissues. The mutant proteins expressed in cultured cells were unstable and causing reduced current density as analyzed by whole-cell patch-clamp technique. Thus, loss-of-function mutations of SCN10A were associated with KSD in the families studied.
URI: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85049795338&origin=inward
http://repository.li.mahidol.ac.th/dspace/handle/123456789/47483
ISSN: 20452322
Appears in Collections:Scopus 2018

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