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Hailey-Hailey disease is caused by mutations in ATP2C1 encoding a novel Ca2+ pump

Hailey-Hailey disease is caused by mutations in ATP2C1 encoding a novel Ca2+ pump
Hailey-Hailey disease is caused by mutations in ATP2C1 encoding a novel Ca2+ pump
Hailey–Hailey disease (HHD) is an autosomal dominant skin disorder characterized by suprabasal cell separation (acantholysis) of the epidermis. Previous genetic linkage studies localized the gene to a 5 cM interval on human chromosome 3q21. After reducing the disease critical region to <1 cM, we used a positional cloning strategy to identify the gene ATP2C1, which is mutated in HHD. ATP2C1 encodes a new class of P-type Ca2+-transport ATPase, which is the homologue for the rat SPLA and the yeast PMR1 medial Golgi Ca2+ pumps and is related to the sarco(endo)plasmic calcium ATPase (SERCA) and plasma membrane calcium ATPase (PCMA) families of Ca2+ pumps. The predicted protein has the same apparent transmembrane organization and contains all of the conserved domains present in other P-type ATPases. ATP2C1 produces two alternative splice variants of ?4.5 kb encoding predicted proteins of 903 and 923 amino acids. We identified 13 different mutations, including nonsense, frameshift insertion and deletions, splice-site mutations, and non-conservative missense mutations. This study dem? onstrates that defects in ATP2C1 cause HHD and together with the recent identification of ATP2A2 as the defective gene in Darier’s disease, provide further evidence of the critical role of Ca2+ signaling in maintaining epidermal integrity.
1131-1140
Sudbrack, Ralf
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Brown, Joanna
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Dobson-Stone, Carol
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Carter, Simon
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Ramser, Juliane
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White, Jacqueline
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Healy, Eugene
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Dissanayake, Manuel
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Larrègue, Marc
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Perrussel, Marc
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Lehrach, Hans
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Munro, Colin S.
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Strachan, Tom
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Burge, Susan
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Hovnanian, Alain
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Monaco, Anthony P.
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Sudbrack, Ralf
e4c7bf2a-dc66-45a4-a3be-cc3e873d4148
Brown, Joanna
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Dobson-Stone, Carol
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Carter, Simon
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Ramser, Juliane
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White, Jacqueline
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Healy, Eugene
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Dissanayake, Manuel
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Larrègue, Marc
182127ff-7dc6-48fb-a5cc-c165d0a44430
Perrussel, Marc
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Lehrach, Hans
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Munro, Colin S.
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Strachan, Tom
9ab590c0-9f84-43f4-8bf3-0946c7925594
Burge, Susan
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Hovnanian, Alain
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Monaco, Anthony P.
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Sudbrack, Ralf, Brown, Joanna, Dobson-Stone, Carol, Carter, Simon, Ramser, Juliane, White, Jacqueline, Healy, Eugene, Dissanayake, Manuel, Larrègue, Marc, Perrussel, Marc, Lehrach, Hans, Munro, Colin S., Strachan, Tom, Burge, Susan, Hovnanian, Alain and Monaco, Anthony P. (2000) Hailey-Hailey disease is caused by mutations in ATP2C1 encoding a novel Ca2+ pump. Human Molecular Genetics, 9 (7), 1131-1140. (doi:10.1093/hmg/9.7.1131).

Record type: Article

Abstract

Hailey–Hailey disease (HHD) is an autosomal dominant skin disorder characterized by suprabasal cell separation (acantholysis) of the epidermis. Previous genetic linkage studies localized the gene to a 5 cM interval on human chromosome 3q21. After reducing the disease critical region to <1 cM, we used a positional cloning strategy to identify the gene ATP2C1, which is mutated in HHD. ATP2C1 encodes a new class of P-type Ca2+-transport ATPase, which is the homologue for the rat SPLA and the yeast PMR1 medial Golgi Ca2+ pumps and is related to the sarco(endo)plasmic calcium ATPase (SERCA) and plasma membrane calcium ATPase (PCMA) families of Ca2+ pumps. The predicted protein has the same apparent transmembrane organization and contains all of the conserved domains present in other P-type ATPases. ATP2C1 produces two alternative splice variants of ?4.5 kb encoding predicted proteins of 903 and 923 amino acids. We identified 13 different mutations, including nonsense, frameshift insertion and deletions, splice-site mutations, and non-conservative missense mutations. This study dem? onstrates that defects in ATP2C1 cause HHD and together with the recent identification of ATP2A2 as the defective gene in Darier’s disease, provide further evidence of the critical role of Ca2+ signaling in maintaining epidermal integrity.

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Published date: 12 April 2000
Organisations: Clinical & Experimental Sciences

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Local EPrints ID: 334306
URI: https://eprints.soton.ac.uk/id/eprint/334306
PURE UUID: 063afe18-fdff-451c-aba5-291cd01ed641

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Date deposited: 07 Mar 2012 11:47
Last modified: 18 Jul 2017 06:12

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Contributors

Author: Ralf Sudbrack
Author: Joanna Brown
Author: Carol Dobson-Stone
Author: Simon Carter
Author: Juliane Ramser
Author: Jacqueline White
Author: Eugene Healy
Author: Manuel Dissanayake
Author: Marc Larrègue
Author: Marc Perrussel
Author: Hans Lehrach
Author: Colin S. Munro
Author: Tom Strachan
Author: Susan Burge
Author: Alain Hovnanian
Author: Anthony P. Monaco

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