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Loss of LDAH associated with prostate cancer and hearing loss.

Publication ,  Journal Article
Currall, BB; Chen, M; Sallari, RC; Cotter, M; Wong, KE; Robertson, NG; Penney, KL; Lunardi, A; Reschke, M; Hickox, AE; Yin, Y; Wong, GT ...
Published in: Hum Mol Genet
December 15, 2018

Great strides in gene discovery have been made using a multitude of methods to associate phenotypes with genetic variants, but there still remains a substantial gap between observed symptoms and identified genetic defects. Herein, we use the convergence of various genetic and genomic techniques to investigate the underpinnings of a constellation of phenotypes that include prostate cancer (PCa) and sensorineural hearing loss (SNHL) in a human subject. Through interrogation of the subject's de novo, germline, balanced chromosomal translocation, we first identify a correlation between his disorders and a poorly annotated gene known as lipid droplet associated hydrolase (LDAH). Using data repositories of both germline and somatic variants, we identify convergent genomic evidence that substantiates a correlation between loss of LDAH and PCa. This correlation is validated through both in vitro and in vivo models that show loss of LDAH results in increased risk of PCa and, to a lesser extent, SNHL. By leveraging convergent evidence in emerging genomic data, we hypothesize that loss of LDAH is involved in PCa and other phenotypes observed in support of a genotype-phenotype association in an n-of-one human subject.

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Published In

Hum Mol Genet

DOI

EISSN

1460-2083

Publication Date

December 15, 2018

Volume

27

Issue

24

Start / End Page

4194 / 4203

Location

England

Related Subject Headings

  • Translocation, Genetic
  • Serine Proteases
  • Prostatic Neoplasms
  • Phenotype
  • Mice, Knockout
  • Mice
  • Male
  • Humans
  • Hearing Loss, Sensorineural
  • Germ Cells
 

Citation

APA
Chicago
ICMJE
MLA
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Currall, B. B., Chen, M., Sallari, R. C., Cotter, M., Wong, K. E., Robertson, N. G., … Morton, C. C. (2018). Loss of LDAH associated with prostate cancer and hearing loss. Hum Mol Genet, 27(24), 4194–4203. https://doi.org/10.1093/hmg/ddy310
Currall, Benjamin B., Ming Chen, Richard C. Sallari, Maura Cotter, Kristen E. Wong, Nahid G. Robertson, Kathryn L. Penney, et al. “Loss of LDAH associated with prostate cancer and hearing loss.Hum Mol Genet 27, no. 24 (December 15, 2018): 4194–4203. https://doi.org/10.1093/hmg/ddy310.
Currall BB, Chen M, Sallari RC, Cotter M, Wong KE, Robertson NG, et al. Loss of LDAH associated with prostate cancer and hearing loss. Hum Mol Genet. 2018 Dec 15;27(24):4194–203.
Currall, Benjamin B., et al. “Loss of LDAH associated with prostate cancer and hearing loss.Hum Mol Genet, vol. 27, no. 24, Dec. 2018, pp. 4194–203. Pubmed, doi:10.1093/hmg/ddy310.
Currall BB, Chen M, Sallari RC, Cotter M, Wong KE, Robertson NG, Penney KL, Lunardi A, Reschke M, Hickox AE, Yin Y, Wong GT, Fung J, Brown KK, Williamson RE, Sinnott-Armstrong NA, Kammin T, Ivanov A, Zepeda-Mendoza CJ, Shen J, Quade BJ, Signoretti S, Arnos KS, Banks AS, Patsopoulos N, Liberman MC, Kellis M, Pandolfi PP, Morton CC. Loss of LDAH associated with prostate cancer and hearing loss. Hum Mol Genet. 2018 Dec 15;27(24):4194–4203.
Journal cover image

Published In

Hum Mol Genet

DOI

EISSN

1460-2083

Publication Date

December 15, 2018

Volume

27

Issue

24

Start / End Page

4194 / 4203

Location

England

Related Subject Headings

  • Translocation, Genetic
  • Serine Proteases
  • Prostatic Neoplasms
  • Phenotype
  • Mice, Knockout
  • Mice
  • Male
  • Humans
  • Hearing Loss, Sensorineural
  • Germ Cells