Perrault syndrome is caused by recessive mutations in CLPP, encoding a mitochondrial ATP-dependent chambered proteaseCitation formats

  • External authors:
  • Atteeq U. Rehman
  • Tom Walsh
  • Jill Clayton-Smith
  • Kwanghyuk Lee
  • Robert J. Morell
  • Meghan C. Drummond
  • Shaheen N. Khan
  • Muhammad Asif Naeem
  • Bushra Rauf
  • Neil Billington
  • Julie M. Schultz
  • Jill E. Urquhart
  • Ming K. Lee
  • Andrew Berry
  • Sarju Mehta
  • Deirdre Cilliers
  • Helen Kingston
  • Thomas T. Warner
  • Dorothy Trump
  • Julian R E Davis
  • Wasim Ahmad
  • Suzanne M. Leal
  • Sheikh Riazuddin
  • Mary Claire King
  • Thomas B. Friedman
  • William G. Newman

Standard

Perrault syndrome is caused by recessive mutations in CLPP, encoding a mitochondrial ATP-dependent chambered protease. / Jenkinson, Emma M.; Rehman, Atteeq U.; Walsh, Tom; Clayton-Smith, Jill; Lee, Kwanghyuk; Morell, Robert J.; Drummond, Meghan C.; Khan, Shaheen N.; Naeem, Muhammad Asif; Rauf, Bushra; Billington, Neil; Schultz, Julie M.; Urquhart, Jill E.; Lee, Ming K.; Berry, Andrew; Hanley, Neil A.; Mehta, Sarju; Cilliers, Deirdre; Clayton, Peter E.; Kingston, Helen; Smith, Miriam J.; Warner, Thomas T.; Black, Graeme C.; Trump, Dorothy; Davis, Julian R E; Ahmad, Wasim; Leal, Suzanne M.; Riazuddin, Sheikh; King, Mary Claire; Friedman, Thomas B.; Newman, William G.

In: American Journal of Human Genetics, Vol. 92, No. 4, 04.04.2013, p. 605-613.

Research output: Contribution to journalArticle

Harvard

Jenkinson, EM, Rehman, AU, Walsh, T, Clayton-Smith, J, Lee, K, Morell, RJ, Drummond, MC, Khan, SN, Naeem, MA, Rauf, B, Billington, N, Schultz, JM, Urquhart, JE, Lee, MK, Berry, A, Hanley, NA, Mehta, S, Cilliers, D, Clayton, PE, Kingston, H, Smith, MJ, Warner, TT, Black, GC, Trump, D, Davis, JRE, Ahmad, W, Leal, SM, Riazuddin, S, King, MC, Friedman, TB & Newman, WG 2013, 'Perrault syndrome is caused by recessive mutations in CLPP, encoding a mitochondrial ATP-dependent chambered protease' American Journal of Human Genetics, vol. 92, no. 4, pp. 605-613. https://doi.org/10.1016/j.ajhg.2013.02.013

APA

Jenkinson, E. M., Rehman, A. U., Walsh, T., Clayton-Smith, J., Lee, K., Morell, R. J., ... Newman, W. G. (2013). Perrault syndrome is caused by recessive mutations in CLPP, encoding a mitochondrial ATP-dependent chambered protease. American Journal of Human Genetics, 92(4), 605-613. https://doi.org/10.1016/j.ajhg.2013.02.013

Vancouver

Jenkinson EM, Rehman AU, Walsh T, Clayton-Smith J, Lee K, Morell RJ et al. Perrault syndrome is caused by recessive mutations in CLPP, encoding a mitochondrial ATP-dependent chambered protease. American Journal of Human Genetics. 2013 Apr 4;92(4):605-613. https://doi.org/10.1016/j.ajhg.2013.02.013

Author

Jenkinson, Emma M. ; Rehman, Atteeq U. ; Walsh, Tom ; Clayton-Smith, Jill ; Lee, Kwanghyuk ; Morell, Robert J. ; Drummond, Meghan C. ; Khan, Shaheen N. ; Naeem, Muhammad Asif ; Rauf, Bushra ; Billington, Neil ; Schultz, Julie M. ; Urquhart, Jill E. ; Lee, Ming K. ; Berry, Andrew ; Hanley, Neil A. ; Mehta, Sarju ; Cilliers, Deirdre ; Clayton, Peter E. ; Kingston, Helen ; Smith, Miriam J. ; Warner, Thomas T. ; Black, Graeme C. ; Trump, Dorothy ; Davis, Julian R E ; Ahmad, Wasim ; Leal, Suzanne M. ; Riazuddin, Sheikh ; King, Mary Claire ; Friedman, Thomas B. ; Newman, William G. / Perrault syndrome is caused by recessive mutations in CLPP, encoding a mitochondrial ATP-dependent chambered protease. In: American Journal of Human Genetics. 2013 ; Vol. 92, No. 4. pp. 605-613.

Bibtex

@article{ee3718e39d254e368fd60fe8cc104895,
title = "Perrault syndrome is caused by recessive mutations in CLPP, encoding a mitochondrial ATP-dependent chambered protease",
abstract = "Perrault syndrome is a genetically and clinically heterogeneous autosomal-recessive condition characterized by sensorineural hearing loss and ovarian failure. By a combination of linkage analysis, homozygosity mapping, and exome sequencing in three families, we identified mutations in CLPP as the likely cause of this phenotype. In each family, affected individuals were homozygous for a different pathogenic CLPP allele: c.433A>C (p.Thr145Pro), c.440G>C (p.Cys147Ser), or an experimentally demonstrated splice-donor-site mutation, c.270+4A>G. CLPP, a component of a mitochondrial ATP-dependent proteolytic complex, is a highly conserved endopeptidase encoded by CLPP and forms an element of the evolutionarily ancient mitochondrial unfolded-protein response (UPRmt) stress signaling pathway. Crystal-structure modeling suggests that both substitutions would alter the structure of the CLPP barrel chamber that captures unfolded proteins and exposes them to proteolysis. Together with the previous identification of mutations in HARS2, encoding mitochondrial histidyl-tRNA synthetase, mutations in CLPP expose dysfunction of mitochondrial protein homeostasis as a cause of Perrault syndrome. {\circledC} 2013 The American Society of Human Genetics.",
keywords = "ATP-Dependent Proteases/*genetics/metabolism, Adenosine Triphosphate/metabolism, Adolescent, Adult, Endopeptidase Clp/*genetics, Exome/*genetics, Female, *Genes, Recessive, Gonadal Dysgenesis, 46,XX/*etiology, Hearing Loss, Sensorineural/*etiology, Homozygote, Humans, In Situ Hybridization, Male, Mitochondria/*enzymology/genetics, Mutation/*genetics, Pedigree, Phenotype, Young Adult",
author = "Jenkinson, {Emma M.} and Rehman, {Atteeq U.} and Tom Walsh and Jill Clayton-Smith and Kwanghyuk Lee and Morell, {Robert J.} and Drummond, {Meghan C.} and Khan, {Shaheen N.} and Naeem, {Muhammad Asif} and Bushra Rauf and Neil Billington and Schultz, {Julie M.} and Urquhart, {Jill E.} and Lee, {Ming K.} and Andrew Berry and Hanley, {Neil A.} and Sarju Mehta and Deirdre Cilliers and Clayton, {Peter E.} and Helen Kingston and Smith, {Miriam J.} and Warner, {Thomas T.} and Black, {Graeme C.} and Dorothy Trump and Davis, {Julian R E} and Wasim Ahmad and Leal, {Suzanne M.} and Sheikh Riazuddin and King, {Mary Claire} and Friedman, {Thomas B.} and Newman, {William G.}",
note = "DC000039-15, NIDCD NIH HHS, United StatesHL004232, NHLBI NIH HHS, United StatesN01 HG065403, NHGRI NIH HHS, United StatesN01-HG-65403, NHGRI NIH HHS, United StatesR01 DC003594, NIDCD NIH HHS, United StatesR01 DC005641, NIDCD NIH HHS, United StatesR01 DC011651, NIDCD NIH HHS, United StatesU54 HG006493, NHGRI NIH HHS, United States, Wellcome Trust, United Kingdom",
year = "2013",
month = "4",
day = "4",
doi = "10.1016/j.ajhg.2013.02.013",
language = "English",
volume = "92",
pages = "605--613",
journal = "Am J Hum Genet",
issn = "0002-9297",
publisher = "Cell Press",
number = "4",

}

RIS

TY - JOUR

T1 - Perrault syndrome is caused by recessive mutations in CLPP, encoding a mitochondrial ATP-dependent chambered protease

AU - Jenkinson, Emma M.

AU - Rehman, Atteeq U.

AU - Walsh, Tom

AU - Clayton-Smith, Jill

AU - Lee, Kwanghyuk

AU - Morell, Robert J.

AU - Drummond, Meghan C.

AU - Khan, Shaheen N.

AU - Naeem, Muhammad Asif

AU - Rauf, Bushra

AU - Billington, Neil

AU - Schultz, Julie M.

AU - Urquhart, Jill E.

AU - Lee, Ming K.

AU - Berry, Andrew

AU - Hanley, Neil A.

AU - Mehta, Sarju

AU - Cilliers, Deirdre

AU - Clayton, Peter E.

AU - Kingston, Helen

AU - Smith, Miriam J.

AU - Warner, Thomas T.

AU - Black, Graeme C.

AU - Trump, Dorothy

AU - Davis, Julian R E

AU - Ahmad, Wasim

AU - Leal, Suzanne M.

AU - Riazuddin, Sheikh

AU - King, Mary Claire

AU - Friedman, Thomas B.

AU - Newman, William G.

N1 - DC000039-15, NIDCD NIH HHS, United StatesHL004232, NHLBI NIH HHS, United StatesN01 HG065403, NHGRI NIH HHS, United StatesN01-HG-65403, NHGRI NIH HHS, United StatesR01 DC003594, NIDCD NIH HHS, United StatesR01 DC005641, NIDCD NIH HHS, United StatesR01 DC011651, NIDCD NIH HHS, United StatesU54 HG006493, NHGRI NIH HHS, United States, Wellcome Trust, United Kingdom

PY - 2013/4/4

Y1 - 2013/4/4

N2 - Perrault syndrome is a genetically and clinically heterogeneous autosomal-recessive condition characterized by sensorineural hearing loss and ovarian failure. By a combination of linkage analysis, homozygosity mapping, and exome sequencing in three families, we identified mutations in CLPP as the likely cause of this phenotype. In each family, affected individuals were homozygous for a different pathogenic CLPP allele: c.433A>C (p.Thr145Pro), c.440G>C (p.Cys147Ser), or an experimentally demonstrated splice-donor-site mutation, c.270+4A>G. CLPP, a component of a mitochondrial ATP-dependent proteolytic complex, is a highly conserved endopeptidase encoded by CLPP and forms an element of the evolutionarily ancient mitochondrial unfolded-protein response (UPRmt) stress signaling pathway. Crystal-structure modeling suggests that both substitutions would alter the structure of the CLPP barrel chamber that captures unfolded proteins and exposes them to proteolysis. Together with the previous identification of mutations in HARS2, encoding mitochondrial histidyl-tRNA synthetase, mutations in CLPP expose dysfunction of mitochondrial protein homeostasis as a cause of Perrault syndrome. © 2013 The American Society of Human Genetics.

AB - Perrault syndrome is a genetically and clinically heterogeneous autosomal-recessive condition characterized by sensorineural hearing loss and ovarian failure. By a combination of linkage analysis, homozygosity mapping, and exome sequencing in three families, we identified mutations in CLPP as the likely cause of this phenotype. In each family, affected individuals were homozygous for a different pathogenic CLPP allele: c.433A>C (p.Thr145Pro), c.440G>C (p.Cys147Ser), or an experimentally demonstrated splice-donor-site mutation, c.270+4A>G. CLPP, a component of a mitochondrial ATP-dependent proteolytic complex, is a highly conserved endopeptidase encoded by CLPP and forms an element of the evolutionarily ancient mitochondrial unfolded-protein response (UPRmt) stress signaling pathway. Crystal-structure modeling suggests that both substitutions would alter the structure of the CLPP barrel chamber that captures unfolded proteins and exposes them to proteolysis. Together with the previous identification of mutations in HARS2, encoding mitochondrial histidyl-tRNA synthetase, mutations in CLPP expose dysfunction of mitochondrial protein homeostasis as a cause of Perrault syndrome. © 2013 The American Society of Human Genetics.

KW - ATP-Dependent Proteases/genetics/metabolism

KW - Adenosine Triphosphate/metabolism

KW - Adolescent

KW - Adult

KW - Endopeptidase Clp/genetics

KW - Exome/genetics

KW - Female

KW - Genes, Recessive

KW - Gonadal Dysgenesis, 46,XX/etiology

KW - Hearing Loss, Sensorineural/etiology

KW - Homozygote

KW - Humans

KW - In Situ Hybridization

KW - Male

KW - Mitochondria/enzymology/genetics

KW - Mutation/genetics

KW - Pedigree

KW - Phenotype

KW - Young Adult

U2 - 10.1016/j.ajhg.2013.02.013

DO - 10.1016/j.ajhg.2013.02.013

M3 - Article

VL - 92

SP - 605

EP - 613

JO - Am J Hum Genet

JF - Am J Hum Genet

SN - 0002-9297

IS - 4

ER -