Genotype-phenotype correlation of a pyridoxine-responsive form of gyrate atrophy

Yukihiko Mashima, Richard G. Weleber, Nancy G. Kennaway, George Inana

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Two clinical subtypes of gyrate atrophy (GA) have been defined based on in-vivo or in-vitro evidence of response to vitamin B6 (pyridoxine), which is the cofactor of the enzyme ornithine aminotransferase (OAT) shown to be defective in GA. We identified the E318K mutation in the OAT gene, heterozygously in three patients and homozygously in one patient, all of whom were vitamin B6-responsive by previous in-vivo and in-vitro studies. Dose-dependent effects of the E318K mutation were observed in the homo- and heterozygotes in the OAT activity, increase of OAT activity in the presence of pyridoxal USA phosphate, and apparent Km for pyridoxal phosphate. The highest residual level of OAT activity and mildness of clinical disease correlated directly with the dose of the mutant E318K allele present in the patient.

Original languageEnglish
Pages (from-to)219-224
Number of pages6
JournalOphthalmic Genetics
Volume20
Issue number4
StatePublished - Dec 1 1999

Fingerprint

Gyrate Atrophy
Ornithine-Oxo-Acid Transaminase
Pyridoxine
Genetic Association Studies
Vitamin B 6
Pyridoxal Phosphate
Mutation
Coenzymes
Homozygote
Heterozygote
Alleles
Genes

Keywords

  • Genotype-phenotype correlation
  • Gyrate atrophy
  • Ornithine aminotransferase
  • Viatmin B6 responsive

ASJC Scopus subject areas

  • Ophthalmology
  • Pediatrics, Perinatology, and Child Health
  • Genetics(clinical)

Cite this

Genotype-phenotype correlation of a pyridoxine-responsive form of gyrate atrophy. / Mashima, Yukihiko; Weleber, Richard G.; Kennaway, Nancy G.; Inana, George.

In: Ophthalmic Genetics, Vol. 20, No. 4, 01.12.1999, p. 219-224.

Research output: Contribution to journalArticle

Mashima, Y, Weleber, RG, Kennaway, NG & Inana, G 1999, 'Genotype-phenotype correlation of a pyridoxine-responsive form of gyrate atrophy', Ophthalmic Genetics, vol. 20, no. 4, pp. 219-224.
Mashima, Yukihiko ; Weleber, Richard G. ; Kennaway, Nancy G. ; Inana, George. / Genotype-phenotype correlation of a pyridoxine-responsive form of gyrate atrophy. In: Ophthalmic Genetics. 1999 ; Vol. 20, No. 4. pp. 219-224.
@article{64c5ada27aab411bad917e465aaf52dc,
title = "Genotype-phenotype correlation of a pyridoxine-responsive form of gyrate atrophy",
abstract = "Two clinical subtypes of gyrate atrophy (GA) have been defined based on in-vivo or in-vitro evidence of response to vitamin B6 (pyridoxine), which is the cofactor of the enzyme ornithine aminotransferase (OAT) shown to be defective in GA. We identified the E318K mutation in the OAT gene, heterozygously in three patients and homozygously in one patient, all of whom were vitamin B6-responsive by previous in-vivo and in-vitro studies. Dose-dependent effects of the E318K mutation were observed in the homo- and heterozygotes in the OAT activity, increase of OAT activity in the presence of pyridoxal USA phosphate, and apparent Km for pyridoxal phosphate. The highest residual level of OAT activity and mildness of clinical disease correlated directly with the dose of the mutant E318K allele present in the patient.",
keywords = "Genotype-phenotype correlation, Gyrate atrophy, Ornithine aminotransferase, Viatmin B6 responsive",
author = "Yukihiko Mashima and Weleber, {Richard G.} and Kennaway, {Nancy G.} and George Inana",
year = "1999",
month = "12",
day = "1",
language = "English",
volume = "20",
pages = "219--224",
journal = "Ophthalmic Genetics",
issn = "0167-6784",
publisher = "Aeolus Press",
number = "4",

}

TY - JOUR

T1 - Genotype-phenotype correlation of a pyridoxine-responsive form of gyrate atrophy

AU - Mashima, Yukihiko

AU - Weleber, Richard G.

AU - Kennaway, Nancy G.

AU - Inana, George

PY - 1999/12/1

Y1 - 1999/12/1

N2 - Two clinical subtypes of gyrate atrophy (GA) have been defined based on in-vivo or in-vitro evidence of response to vitamin B6 (pyridoxine), which is the cofactor of the enzyme ornithine aminotransferase (OAT) shown to be defective in GA. We identified the E318K mutation in the OAT gene, heterozygously in three patients and homozygously in one patient, all of whom were vitamin B6-responsive by previous in-vivo and in-vitro studies. Dose-dependent effects of the E318K mutation were observed in the homo- and heterozygotes in the OAT activity, increase of OAT activity in the presence of pyridoxal USA phosphate, and apparent Km for pyridoxal phosphate. The highest residual level of OAT activity and mildness of clinical disease correlated directly with the dose of the mutant E318K allele present in the patient.

AB - Two clinical subtypes of gyrate atrophy (GA) have been defined based on in-vivo or in-vitro evidence of response to vitamin B6 (pyridoxine), which is the cofactor of the enzyme ornithine aminotransferase (OAT) shown to be defective in GA. We identified the E318K mutation in the OAT gene, heterozygously in three patients and homozygously in one patient, all of whom were vitamin B6-responsive by previous in-vivo and in-vitro studies. Dose-dependent effects of the E318K mutation were observed in the homo- and heterozygotes in the OAT activity, increase of OAT activity in the presence of pyridoxal USA phosphate, and apparent Km for pyridoxal phosphate. The highest residual level of OAT activity and mildness of clinical disease correlated directly with the dose of the mutant E318K allele present in the patient.

KW - Genotype-phenotype correlation

KW - Gyrate atrophy

KW - Ornithine aminotransferase

KW - Viatmin B6 responsive

UR - http://www.scopus.com/inward/record.url?scp=0033383021&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033383021&partnerID=8YFLogxK

M3 - Article

C2 - 10617919

AN - SCOPUS:0033383021

VL - 20

SP - 219

EP - 224

JO - Ophthalmic Genetics

JF - Ophthalmic Genetics

SN - 0167-6784

IS - 4

ER -