A de novo MYOC mutation detected in juvenile open angle glaucoma associated with reduced myocilin protein in aqueous humor

John Kuchtey, Uttio Roy Chowdhury, Colby C. Uptegraft, Michael P Fautsch, Rachel W. Kuchtey

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

MYOC mutations were originally identified in patients with juvenile open angle glaucoma (JOAG). Cell culture and mouse studies suggest that MYOC mutations cause glaucoma through a dominant-negative effect on myocilin protein secretion. We tested this hypothesis with patient samples in this study. Glaucoma and control patients underwent complete ocular examination. DNA samples from glaucoma patients, unaffected relatives and controls were used for DNA sequencing of MYOC. Aqueous humor (AH) samples from glaucoma and control patients were obtained at the time of surgery. Myocilin protein in AH was detected by quantitative Western blot analysis. A de novo Val251Ala mutation of MYOC was found to segregate with disease in a family with autosomal dominant JOAG. Myocilin protein was detected in all control AH samples but was nearly undetectable in AH samples from a patient heterozygous for the Val251Ala mutation. Our results using human patient samples are consistent with a dominant-negative effect of pathogenic MYOC mutations on myocilin secretion.

Original languageEnglish (US)
Pages (from-to)292-296
Number of pages5
JournalEuropean Journal of Medical Genetics
Volume56
Issue number6
DOIs
StatePublished - Jun 2013

Fingerprint

Aqueous Humor
Open Angle Glaucoma
Mutation
Glaucoma
Proteins
trabecular meshwork-induced glucocorticoid response protein
DNA Sequence Analysis
Cell Culture Techniques
Western Blotting
DNA

Keywords

  • Aqueous humor
  • De novo mutation
  • Glaucoma
  • Myocilin

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

A de novo MYOC mutation detected in juvenile open angle glaucoma associated with reduced myocilin protein in aqueous humor. / Kuchtey, John; Chowdhury, Uttio Roy; Uptegraft, Colby C.; Fautsch, Michael P; Kuchtey, Rachel W.

In: European Journal of Medical Genetics, Vol. 56, No. 6, 06.2013, p. 292-296.

Research output: Contribution to journalArticle

Kuchtey, John ; Chowdhury, Uttio Roy ; Uptegraft, Colby C. ; Fautsch, Michael P ; Kuchtey, Rachel W. / A de novo MYOC mutation detected in juvenile open angle glaucoma associated with reduced myocilin protein in aqueous humor. In: European Journal of Medical Genetics. 2013 ; Vol. 56, No. 6. pp. 292-296.
@article{11ff3bb617c54a3ab5daf104feff7a73,
title = "A de novo MYOC mutation detected in juvenile open angle glaucoma associated with reduced myocilin protein in aqueous humor",
abstract = "MYOC mutations were originally identified in patients with juvenile open angle glaucoma (JOAG). Cell culture and mouse studies suggest that MYOC mutations cause glaucoma through a dominant-negative effect on myocilin protein secretion. We tested this hypothesis with patient samples in this study. Glaucoma and control patients underwent complete ocular examination. DNA samples from glaucoma patients, unaffected relatives and controls were used for DNA sequencing of MYOC. Aqueous humor (AH) samples from glaucoma and control patients were obtained at the time of surgery. Myocilin protein in AH was detected by quantitative Western blot analysis. A de novo Val251Ala mutation of MYOC was found to segregate with disease in a family with autosomal dominant JOAG. Myocilin protein was detected in all control AH samples but was nearly undetectable in AH samples from a patient heterozygous for the Val251Ala mutation. Our results using human patient samples are consistent with a dominant-negative effect of pathogenic MYOC mutations on myocilin secretion.",
keywords = "Aqueous humor, De novo mutation, Glaucoma, Myocilin",
author = "John Kuchtey and Chowdhury, {Uttio Roy} and Uptegraft, {Colby C.} and Fautsch, {Michael P} and Kuchtey, {Rachel W.}",
year = "2013",
month = "6",
doi = "10.1016/j.ejmg.2013.03.002",
language = "English (US)",
volume = "56",
pages = "292--296",
journal = "European Journal of Medical Genetics",
issn = "1769-7212",
publisher = "Elsevier Masson SAS",
number = "6",

}

TY - JOUR

T1 - A de novo MYOC mutation detected in juvenile open angle glaucoma associated with reduced myocilin protein in aqueous humor

AU - Kuchtey, John

AU - Chowdhury, Uttio Roy

AU - Uptegraft, Colby C.

AU - Fautsch, Michael P

AU - Kuchtey, Rachel W.

PY - 2013/6

Y1 - 2013/6

N2 - MYOC mutations were originally identified in patients with juvenile open angle glaucoma (JOAG). Cell culture and mouse studies suggest that MYOC mutations cause glaucoma through a dominant-negative effect on myocilin protein secretion. We tested this hypothesis with patient samples in this study. Glaucoma and control patients underwent complete ocular examination. DNA samples from glaucoma patients, unaffected relatives and controls were used for DNA sequencing of MYOC. Aqueous humor (AH) samples from glaucoma and control patients were obtained at the time of surgery. Myocilin protein in AH was detected by quantitative Western blot analysis. A de novo Val251Ala mutation of MYOC was found to segregate with disease in a family with autosomal dominant JOAG. Myocilin protein was detected in all control AH samples but was nearly undetectable in AH samples from a patient heterozygous for the Val251Ala mutation. Our results using human patient samples are consistent with a dominant-negative effect of pathogenic MYOC mutations on myocilin secretion.

AB - MYOC mutations were originally identified in patients with juvenile open angle glaucoma (JOAG). Cell culture and mouse studies suggest that MYOC mutations cause glaucoma through a dominant-negative effect on myocilin protein secretion. We tested this hypothesis with patient samples in this study. Glaucoma and control patients underwent complete ocular examination. DNA samples from glaucoma patients, unaffected relatives and controls were used for DNA sequencing of MYOC. Aqueous humor (AH) samples from glaucoma and control patients were obtained at the time of surgery. Myocilin protein in AH was detected by quantitative Western blot analysis. A de novo Val251Ala mutation of MYOC was found to segregate with disease in a family with autosomal dominant JOAG. Myocilin protein was detected in all control AH samples but was nearly undetectable in AH samples from a patient heterozygous for the Val251Ala mutation. Our results using human patient samples are consistent with a dominant-negative effect of pathogenic MYOC mutations on myocilin secretion.

KW - Aqueous humor

KW - De novo mutation

KW - Glaucoma

KW - Myocilin

UR - http://www.scopus.com/inward/record.url?scp=84878463314&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84878463314&partnerID=8YFLogxK

U2 - 10.1016/j.ejmg.2013.03.002

DO - 10.1016/j.ejmg.2013.03.002

M3 - Article

VL - 56

SP - 292

EP - 296

JO - European Journal of Medical Genetics

JF - European Journal of Medical Genetics

SN - 1769-7212

IS - 6

ER -