A PRPH splice-donor variant associates with reduced sural nerve amplitude and risk of peripheral neuropathy

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A PRPH splice-donor variant associates with reduced sural nerve amplitude and risk of peripheral neuropathy. / Bjornsdottir, Gyda; Ivarsdottir, Erna V.; Bjarnadottir, Kristbjorg; Benonisdottir, Stefania; Gylfadottir, Sandra Sif; Arnadottir, Gudny A.; Benediktsson, Rafn; Halldorsson, Gisli Hreinn; Helgadottir, Anna; Jonasdottir, Adalbjorg; Jonasdottir, Aslaug; Jonsdottir, Ingileif; Kristinsdottir, Anna Margret; Magnusson, Olafur Th; Masson, Gisli; Melsted, Pall; Rafnar, Thorunn; Sigurdsson, Asgeir; Sigurdsson, Gunnar; Skuladottir, Astros; Steinthorsdottir, Valgerdur; Styrkarsdottir, Unnur; Thorgeirsson, Gudmundur; Thorleifsson, Gudmar; Vikingsson, Arnor; Gudbjartsson, Daniel F.; Holm, Hilma; Stefansson, Hreinn; Thorsteinsdottir, Unnur; Norddahl, Gudmundur L.; Sulem, Patrick; Thorgeirsson, Thorgeir E.; Stefansson, Kari.

In: Nature Communications, Vol. 10, No. 1, 1777, 2019.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Harvard

Bjornsdottir, G, Ivarsdottir, EV, Bjarnadottir, K, Benonisdottir, S, Gylfadottir, SS, Arnadottir, GA, Benediktsson, R, Halldorsson, GH, Helgadottir, A, Jonasdottir, A, Jonasdottir, A, Jonsdottir, I, Kristinsdottir, AM, Magnusson, OT, Masson, G, Melsted, P, Rafnar, T, Sigurdsson, A, Sigurdsson, G, Skuladottir, A, Steinthorsdottir, V, Styrkarsdottir, U, Thorgeirsson, G, Thorleifsson, G, Vikingsson, A, Gudbjartsson, DF, Holm, H, Stefansson, H, Thorsteinsdottir, U, Norddahl, GL, Sulem, P, Thorgeirsson, TE & Stefansson, K 2019, 'A PRPH splice-donor variant associates with reduced sural nerve amplitude and risk of peripheral neuropathy', Nature Communications, vol. 10, no. 1, 1777. https://doi.org/10.1038/s41467-019-09719-4

APA

Bjornsdottir, G., Ivarsdottir, E. V., Bjarnadottir, K., Benonisdottir, S., Gylfadottir, S. S., Arnadottir, G. A., Benediktsson, R., Halldorsson, G. H., Helgadottir, A., Jonasdottir, A., Jonasdottir, A., Jonsdottir, I., Kristinsdottir, A. M., Magnusson, O. T., Masson, G., Melsted, P., Rafnar, T., Sigurdsson, A., Sigurdsson, G., ... Stefansson, K. (2019). A PRPH splice-donor variant associates with reduced sural nerve amplitude and risk of peripheral neuropathy. Nature Communications, 10(1), [1777]. https://doi.org/10.1038/s41467-019-09719-4

CBE

Bjornsdottir G, Ivarsdottir EV, Bjarnadottir K, Benonisdottir S, Gylfadottir SS, Arnadottir GA, Benediktsson R, Halldorsson GH, Helgadottir A, Jonasdottir A, Jonasdottir A, Jonsdottir I, Kristinsdottir AM, Magnusson OT, Masson G, Melsted P, Rafnar T, Sigurdsson A, Sigurdsson G, Skuladottir A, Steinthorsdottir V, Styrkarsdottir U, Thorgeirsson G, Thorleifsson G, Vikingsson A, Gudbjartsson DF, Holm H, Stefansson H, Thorsteinsdottir U, Norddahl GL, Sulem P, Thorgeirsson TE, Stefansson K. 2019. A PRPH splice-donor variant associates with reduced sural nerve amplitude and risk of peripheral neuropathy. Nature Communications. 10(1):Article 1777. https://doi.org/10.1038/s41467-019-09719-4

MLA

Vancouver

Bjornsdottir G, Ivarsdottir EV, Bjarnadottir K, Benonisdottir S, Gylfadottir SS, Arnadottir GA et al. A PRPH splice-donor variant associates with reduced sural nerve amplitude and risk of peripheral neuropathy. Nature Communications. 2019;10(1). 1777. https://doi.org/10.1038/s41467-019-09719-4

Author

Bjornsdottir, Gyda ; Ivarsdottir, Erna V. ; Bjarnadottir, Kristbjorg ; Benonisdottir, Stefania ; Gylfadottir, Sandra Sif ; Arnadottir, Gudny A. ; Benediktsson, Rafn ; Halldorsson, Gisli Hreinn ; Helgadottir, Anna ; Jonasdottir, Adalbjorg ; Jonasdottir, Aslaug ; Jonsdottir, Ingileif ; Kristinsdottir, Anna Margret ; Magnusson, Olafur Th ; Masson, Gisli ; Melsted, Pall ; Rafnar, Thorunn ; Sigurdsson, Asgeir ; Sigurdsson, Gunnar ; Skuladottir, Astros ; Steinthorsdottir, Valgerdur ; Styrkarsdottir, Unnur ; Thorgeirsson, Gudmundur ; Thorleifsson, Gudmar ; Vikingsson, Arnor ; Gudbjartsson, Daniel F. ; Holm, Hilma ; Stefansson, Hreinn ; Thorsteinsdottir, Unnur ; Norddahl, Gudmundur L. ; Sulem, Patrick ; Thorgeirsson, Thorgeir E. ; Stefansson, Kari. / A PRPH splice-donor variant associates with reduced sural nerve amplitude and risk of peripheral neuropathy. In: Nature Communications. 2019 ; Vol. 10, No. 1.

Bibtex

@article{509a157d50a74d03bc918b3705361a2c,
title = "A PRPH splice-donor variant associates with reduced sural nerve amplitude and risk of peripheral neuropathy",
abstract = "Nerve conduction (NC) studies generate measures of peripheral nerve function that can reveal underlying pathology due to axonal loss, demyelination or both. We perform a genome-wide association study of sural NC amplitude and velocity in 7045 Icelanders and find a low-frequency splice-donor variant in PRPH (c.996+1G>A; MAF = 1.32%) associating with decreased NC amplitude but not velocity. PRPH encodes peripherin, an intermediate filament (IF) protein involved in cytoskeletal development and maintenance of neurons. Through RNA and protein studies, we show that the variant leads to loss-of-function (LoF), as when over-expressed in a cell line devoid of other IFs, it does not allow formation of the normal filamentous structure of peripherin, yielding instead punctate protein inclusions. Recall of carriers for neurological assessment confirms that from an early age, homozygotes have significantly lower sural NC amplitude than non-carriers and are at risk of a mild, early-onset, sensory-negative, axonal polyneuropathy.",
author = "Gyda Bjornsdottir and Ivarsdottir, {Erna V.} and Kristbjorg Bjarnadottir and Stefania Benonisdottir and Gylfadottir, {Sandra Sif} and Arnadottir, {Gudny A.} and Rafn Benediktsson and Halldorsson, {Gisli Hreinn} and Anna Helgadottir and Adalbjorg Jonasdottir and Aslaug Jonasdottir and Ingileif Jonsdottir and Kristinsdottir, {Anna Margret} and Magnusson, {Olafur Th} and Gisli Masson and Pall Melsted and Thorunn Rafnar and Asgeir Sigurdsson and Gunnar Sigurdsson and Astros Skuladottir and Valgerdur Steinthorsdottir and Unnur Styrkarsdottir and Gudmundur Thorgeirsson and Gudmar Thorleifsson and Arnor Vikingsson and Gudbjartsson, {Daniel F.} and Hilma Holm and Hreinn Stefansson and Unnur Thorsteinsdottir and Norddahl, {Gudmundur L.} and Patrick Sulem and Thorgeirsson, {Thorgeir E.} and Kari Stefansson",
year = "2019",
doi = "10.1038/s41467-019-09719-4",
language = "English",
volume = "10",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",

}

RIS

TY - JOUR

T1 - A PRPH splice-donor variant associates with reduced sural nerve amplitude and risk of peripheral neuropathy

AU - Bjornsdottir, Gyda

AU - Ivarsdottir, Erna V.

AU - Bjarnadottir, Kristbjorg

AU - Benonisdottir, Stefania

AU - Gylfadottir, Sandra Sif

AU - Arnadottir, Gudny A.

AU - Benediktsson, Rafn

AU - Halldorsson, Gisli Hreinn

AU - Helgadottir, Anna

AU - Jonasdottir, Adalbjorg

AU - Jonasdottir, Aslaug

AU - Jonsdottir, Ingileif

AU - Kristinsdottir, Anna Margret

AU - Magnusson, Olafur Th

AU - Masson, Gisli

AU - Melsted, Pall

AU - Rafnar, Thorunn

AU - Sigurdsson, Asgeir

AU - Sigurdsson, Gunnar

AU - Skuladottir, Astros

AU - Steinthorsdottir, Valgerdur

AU - Styrkarsdottir, Unnur

AU - Thorgeirsson, Gudmundur

AU - Thorleifsson, Gudmar

AU - Vikingsson, Arnor

AU - Gudbjartsson, Daniel F.

AU - Holm, Hilma

AU - Stefansson, Hreinn

AU - Thorsteinsdottir, Unnur

AU - Norddahl, Gudmundur L.

AU - Sulem, Patrick

AU - Thorgeirsson, Thorgeir E.

AU - Stefansson, Kari

PY - 2019

Y1 - 2019

N2 - Nerve conduction (NC) studies generate measures of peripheral nerve function that can reveal underlying pathology due to axonal loss, demyelination or both. We perform a genome-wide association study of sural NC amplitude and velocity in 7045 Icelanders and find a low-frequency splice-donor variant in PRPH (c.996+1G>A; MAF = 1.32%) associating with decreased NC amplitude but not velocity. PRPH encodes peripherin, an intermediate filament (IF) protein involved in cytoskeletal development and maintenance of neurons. Through RNA and protein studies, we show that the variant leads to loss-of-function (LoF), as when over-expressed in a cell line devoid of other IFs, it does not allow formation of the normal filamentous structure of peripherin, yielding instead punctate protein inclusions. Recall of carriers for neurological assessment confirms that from an early age, homozygotes have significantly lower sural NC amplitude than non-carriers and are at risk of a mild, early-onset, sensory-negative, axonal polyneuropathy.

AB - Nerve conduction (NC) studies generate measures of peripheral nerve function that can reveal underlying pathology due to axonal loss, demyelination or both. We perform a genome-wide association study of sural NC amplitude and velocity in 7045 Icelanders and find a low-frequency splice-donor variant in PRPH (c.996+1G>A; MAF = 1.32%) associating with decreased NC amplitude but not velocity. PRPH encodes peripherin, an intermediate filament (IF) protein involved in cytoskeletal development and maintenance of neurons. Through RNA and protein studies, we show that the variant leads to loss-of-function (LoF), as when over-expressed in a cell line devoid of other IFs, it does not allow formation of the normal filamentous structure of peripherin, yielding instead punctate protein inclusions. Recall of carriers for neurological assessment confirms that from an early age, homozygotes have significantly lower sural NC amplitude than non-carriers and are at risk of a mild, early-onset, sensory-negative, axonal polyneuropathy.

UR - http://www.scopus.com/inward/record.url?scp=85064544852&partnerID=8YFLogxK

U2 - 10.1038/s41467-019-09719-4

DO - 10.1038/s41467-019-09719-4

M3 - Journal article

C2 - 30992453

AN - SCOPUS:85064544852

VL - 10

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 1777

ER -