Clinical Features Associated With an Asp380His Myocilin Mutation in a US Family With Primary Open-Angle Glaucoma

Mary Wirtz, John R. Samples, Dongseok Choi, N. Donna Gaudette

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Purpose: To determine the glaucoma phenotype of an American pedigree with the myocilin Asp380His. Design: An observational case series study. Methods: An observational case series study was used to examine a family in which an Asp380His myocilin mutation was segregating. Thirteen family members were examined and medical records were obtained on the remaining two individuals. Blood samples were collected from all 15 participants following the tenets of the Helsinki declaration under the auspices of the Oregon Health & Sciences University Institutional Review Board and screened for myocilin variants by denaturing high-performance liquid chromatography (dHPLC). Any DNA samples with dHPLC data different from the control sample were sequenced for base pair analysis. Results: An Asp380His myocilin mutation was identified in eight members, seven of whom had primary open-angle glaucoma (POAG). The eighth individual had high intraocular pressures (IOPs). The disease presents in this family with extremely high IOPs requiring trabeculectomies to control the pressure. The age at diagnosis ranged from 30 to 45. Conclusions: This family with an Asp380His myocilin mutation presents with an intermediate phenotype between juvenile- and adult-onset glaucoma. The Asp380 amino acid residue appears to be important in myocilin function based on the finding that substitution of this amino acid with four different amino acids (His, Ala, Asn, or Gly) all result in a similar presentation of POAG that is intermediate between the more severe clinical presentations observed in individuals with the Pro370Leu or Lys423Glu variant and the milder findings in patients with the Gln368Stop mutation.

Original languageEnglish (US)
JournalAmerican Journal of Ophthalmology
Volume144
Issue number1
DOIs
StatePublished - Jul 2007

Fingerprint

Mutation
Intraocular Pressure
Glaucoma
Helsinki Declaration
High Pressure Liquid Chromatography
Phenotype
Amino Acids
Trabeculectomy
Research Ethics Committees
Amino Acid Substitution
Pedigree
Base Pairing
Medical Records
trabecular meshwork-induced glucocorticoid response protein
Primary Open Angle Glaucoma
Pressure
DNA
Health

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Clinical Features Associated With an Asp380His Myocilin Mutation in a US Family With Primary Open-Angle Glaucoma. / Wirtz, Mary; Samples, John R.; Choi, Dongseok; Gaudette, N. Donna.

In: American Journal of Ophthalmology, Vol. 144, No. 1, 07.2007.

Research output: Contribution to journalArticle

@article{5aa57b621e794a38b619a7525a33688f,
title = "Clinical Features Associated With an Asp380His Myocilin Mutation in a US Family With Primary Open-Angle Glaucoma",
abstract = "Purpose: To determine the glaucoma phenotype of an American pedigree with the myocilin Asp380His. Design: An observational case series study. Methods: An observational case series study was used to examine a family in which an Asp380His myocilin mutation was segregating. Thirteen family members were examined and medical records were obtained on the remaining two individuals. Blood samples were collected from all 15 participants following the tenets of the Helsinki declaration under the auspices of the Oregon Health & Sciences University Institutional Review Board and screened for myocilin variants by denaturing high-performance liquid chromatography (dHPLC). Any DNA samples with dHPLC data different from the control sample were sequenced for base pair analysis. Results: An Asp380His myocilin mutation was identified in eight members, seven of whom had primary open-angle glaucoma (POAG). The eighth individual had high intraocular pressures (IOPs). The disease presents in this family with extremely high IOPs requiring trabeculectomies to control the pressure. The age at diagnosis ranged from 30 to 45. Conclusions: This family with an Asp380His myocilin mutation presents with an intermediate phenotype between juvenile- and adult-onset glaucoma. The Asp380 amino acid residue appears to be important in myocilin function based on the finding that substitution of this amino acid with four different amino acids (His, Ala, Asn, or Gly) all result in a similar presentation of POAG that is intermediate between the more severe clinical presentations observed in individuals with the Pro370Leu or Lys423Glu variant and the milder findings in patients with the Gln368Stop mutation.",
author = "Mary Wirtz and Samples, {John R.} and Dongseok Choi and Gaudette, {N. Donna}",
year = "2007",
month = "7",
doi = "10.1016/j.ajo.2007.03.037",
language = "English (US)",
volume = "144",
journal = "American Journal of Ophthalmology",
issn = "0002-9394",
publisher = "Elsevier USA",
number = "1",

}

TY - JOUR

T1 - Clinical Features Associated With an Asp380His Myocilin Mutation in a US Family With Primary Open-Angle Glaucoma

AU - Wirtz, Mary

AU - Samples, John R.

AU - Choi, Dongseok

AU - Gaudette, N. Donna

PY - 2007/7

Y1 - 2007/7

N2 - Purpose: To determine the glaucoma phenotype of an American pedigree with the myocilin Asp380His. Design: An observational case series study. Methods: An observational case series study was used to examine a family in which an Asp380His myocilin mutation was segregating. Thirteen family members were examined and medical records were obtained on the remaining two individuals. Blood samples were collected from all 15 participants following the tenets of the Helsinki declaration under the auspices of the Oregon Health & Sciences University Institutional Review Board and screened for myocilin variants by denaturing high-performance liquid chromatography (dHPLC). Any DNA samples with dHPLC data different from the control sample were sequenced for base pair analysis. Results: An Asp380His myocilin mutation was identified in eight members, seven of whom had primary open-angle glaucoma (POAG). The eighth individual had high intraocular pressures (IOPs). The disease presents in this family with extremely high IOPs requiring trabeculectomies to control the pressure. The age at diagnosis ranged from 30 to 45. Conclusions: This family with an Asp380His myocilin mutation presents with an intermediate phenotype between juvenile- and adult-onset glaucoma. The Asp380 amino acid residue appears to be important in myocilin function based on the finding that substitution of this amino acid with four different amino acids (His, Ala, Asn, or Gly) all result in a similar presentation of POAG that is intermediate between the more severe clinical presentations observed in individuals with the Pro370Leu or Lys423Glu variant and the milder findings in patients with the Gln368Stop mutation.

AB - Purpose: To determine the glaucoma phenotype of an American pedigree with the myocilin Asp380His. Design: An observational case series study. Methods: An observational case series study was used to examine a family in which an Asp380His myocilin mutation was segregating. Thirteen family members were examined and medical records were obtained on the remaining two individuals. Blood samples were collected from all 15 participants following the tenets of the Helsinki declaration under the auspices of the Oregon Health & Sciences University Institutional Review Board and screened for myocilin variants by denaturing high-performance liquid chromatography (dHPLC). Any DNA samples with dHPLC data different from the control sample were sequenced for base pair analysis. Results: An Asp380His myocilin mutation was identified in eight members, seven of whom had primary open-angle glaucoma (POAG). The eighth individual had high intraocular pressures (IOPs). The disease presents in this family with extremely high IOPs requiring trabeculectomies to control the pressure. The age at diagnosis ranged from 30 to 45. Conclusions: This family with an Asp380His myocilin mutation presents with an intermediate phenotype between juvenile- and adult-onset glaucoma. The Asp380 amino acid residue appears to be important in myocilin function based on the finding that substitution of this amino acid with four different amino acids (His, Ala, Asn, or Gly) all result in a similar presentation of POAG that is intermediate between the more severe clinical presentations observed in individuals with the Pro370Leu or Lys423Glu variant and the milder findings in patients with the Gln368Stop mutation.

UR - http://www.scopus.com/inward/record.url?scp=34250777931&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34250777931&partnerID=8YFLogxK

U2 - 10.1016/j.ajo.2007.03.037

DO - 10.1016/j.ajo.2007.03.037

M3 - Article

C2 - 17499207

AN - SCOPUS:34250777931

VL - 144

JO - American Journal of Ophthalmology

JF - American Journal of Ophthalmology

SN - 0002-9394

IS - 1

ER -