Molecular analysis of hereditary methemoglobinemia

Jun Lchl Manabe, Roopen Arya, Hideki Sumimoto, Masataka Miyazaki, Toshltsugu Yubisui, D. Mark Layton, Yasuyuki Fukumaki

Research output: Contribution to journalArticle

Abstract

Hereditary methemoglobinemla is an autosomal recessive disorder characterized by NADH-cytochrome bo reductase (b5R) deficiency. This disorder is classified Into two types: an erythrocyte (type I) and a generalized (type II) types. We analyzed the bSRgenes of a patient with type Üfrom a white U. K. family using PCR-related techniques, and found that the patient was a compound hétérozygote for two novel mutations, a nonsense mutation at codon 42 (TAC-TAA) and a mlssense mutation at codon 95 (CCC; Pro-CAC; His). From the allele with the nonsense mutation, the product without the catalytic portion of the enzyme Is generated. To characterize the effect of the missense mutation on the enzyme function, we compared GST-fused b5R with the GST-fused mutant enzyme expressed in Escherichia. call The mutant enzyme exhibited less catalytic activity, less thermostability and more susceptibility to trypsin than did the normal counterpart. The absorption spectrum of the mutant enzyme In the visual region differed from that of the wild type. These results suggested that this amlno acid substitution within the FAD-blnding domain of the enzyme Influences both a secondary structure and a catalytic activity of the enzyme. One Japanese case of type n was also Investigated. A novel nonesense mutation (GAG;Glu-TAG;Stop) was detected In the codon 255 of one allele, however no mutation is observed in another allele. A Greek-Cyprus case with typell, in which no obvious mutation Is associated with the b5R gene, was presented. Possible molecular basis of such cases was discussed.

Original languageEnglish
Number of pages1
JournalJapanese Journal of Human Genetics
Volume42
Issue number1
Publication statusPublished - Dec 1 1997

Fingerprint

Methemoglobinemia
Enzymes
Mutation
Codon
Nonsense Codon
Alleles
Cyprus
Cytochrome Reductases
Escherichia
Flavin-Adenine Dinucleotide
Missense Mutation
NAD
Trypsin
Erythrocytes
Polymerase Chain Reaction
Acids

All Science Journal Classification (ASJC) codes

  • Genetics(clinical)

Cite this

Manabe, J. L., Arya, R., Sumimoto, H., Miyazaki, M., Yubisui, T., Mark Layton, D., & Fukumaki, Y. (1997). Molecular analysis of hereditary methemoglobinemia. Japanese Journal of Human Genetics, 42(1).

Molecular analysis of hereditary methemoglobinemia. / Manabe, Jun Lchl; Arya, Roopen; Sumimoto, Hideki; Miyazaki, Masataka; Yubisui, Toshltsugu; Mark Layton, D.; Fukumaki, Yasuyuki.

In: Japanese Journal of Human Genetics, Vol. 42, No. 1, 01.12.1997.

Research output: Contribution to journalArticle

Manabe, JL, Arya, R, Sumimoto, H, Miyazaki, M, Yubisui, T, Mark Layton, D & Fukumaki, Y 1997, 'Molecular analysis of hereditary methemoglobinemia', Japanese Journal of Human Genetics, vol. 42, no. 1.
Manabe JL, Arya R, Sumimoto H, Miyazaki M, Yubisui T, Mark Layton D et al. Molecular analysis of hereditary methemoglobinemia. Japanese Journal of Human Genetics. 1997 Dec 1;42(1).
Manabe, Jun Lchl ; Arya, Roopen ; Sumimoto, Hideki ; Miyazaki, Masataka ; Yubisui, Toshltsugu ; Mark Layton, D. ; Fukumaki, Yasuyuki. / Molecular analysis of hereditary methemoglobinemia. In: Japanese Journal of Human Genetics. 1997 ; Vol. 42, No. 1.
@article{67544277720c4906b9337968d592bb0b,
title = "Molecular analysis of hereditary methemoglobinemia",
abstract = "Hereditary methemoglobinemla is an autosomal recessive disorder characterized by NADH-cytochrome bo reductase (b5R) deficiency. This disorder is classified Into two types: an erythrocyte (type I) and a generalized (type II) types. We analyzed the bSRgenes of a patient with type {\"U}from a white U. K. family using PCR-related techniques, and found that the patient was a compound h{\'e}t{\'e}rozygote for two novel mutations, a nonsense mutation at codon 42 (TAC-TAA) and a mlssense mutation at codon 95 (CCC; Pro-CAC; His). From the allele with the nonsense mutation, the product without the catalytic portion of the enzyme Is generated. To characterize the effect of the missense mutation on the enzyme function, we compared GST-fused b5R with the GST-fused mutant enzyme expressed in Escherichia. call The mutant enzyme exhibited less catalytic activity, less thermostability and more susceptibility to trypsin than did the normal counterpart. The absorption spectrum of the mutant enzyme In the visual region differed from that of the wild type. These results suggested that this amlno acid substitution within the FAD-blnding domain of the enzyme Influences both a secondary structure and a catalytic activity of the enzyme. One Japanese case of type n was also Investigated. A novel nonesense mutation (GAG;Glu-TAG;Stop) was detected In the codon 255 of one allele, however no mutation is observed in another allele. A Greek-Cyprus case with typell, in which no obvious mutation Is associated with the b5R gene, was presented. Possible molecular basis of such cases was discussed.",
author = "Manabe, {Jun Lchl} and Roopen Arya and Hideki Sumimoto and Masataka Miyazaki and Toshltsugu Yubisui and {Mark Layton}, D. and Yasuyuki Fukumaki",
year = "1997",
month = "12",
day = "1",
language = "English",
volume = "42",
journal = "Journal of Human Genetics",
issn = "1434-5161",
publisher = "Nature Publishing Group",
number = "1",

}

TY - JOUR

T1 - Molecular analysis of hereditary methemoglobinemia

AU - Manabe, Jun Lchl

AU - Arya, Roopen

AU - Sumimoto, Hideki

AU - Miyazaki, Masataka

AU - Yubisui, Toshltsugu

AU - Mark Layton, D.

AU - Fukumaki, Yasuyuki

PY - 1997/12/1

Y1 - 1997/12/1

N2 - Hereditary methemoglobinemla is an autosomal recessive disorder characterized by NADH-cytochrome bo reductase (b5R) deficiency. This disorder is classified Into two types: an erythrocyte (type I) and a generalized (type II) types. We analyzed the bSRgenes of a patient with type Üfrom a white U. K. family using PCR-related techniques, and found that the patient was a compound hétérozygote for two novel mutations, a nonsense mutation at codon 42 (TAC-TAA) and a mlssense mutation at codon 95 (CCC; Pro-CAC; His). From the allele with the nonsense mutation, the product without the catalytic portion of the enzyme Is generated. To characterize the effect of the missense mutation on the enzyme function, we compared GST-fused b5R with the GST-fused mutant enzyme expressed in Escherichia. call The mutant enzyme exhibited less catalytic activity, less thermostability and more susceptibility to trypsin than did the normal counterpart. The absorption spectrum of the mutant enzyme In the visual region differed from that of the wild type. These results suggested that this amlno acid substitution within the FAD-blnding domain of the enzyme Influences both a secondary structure and a catalytic activity of the enzyme. One Japanese case of type n was also Investigated. A novel nonesense mutation (GAG;Glu-TAG;Stop) was detected In the codon 255 of one allele, however no mutation is observed in another allele. A Greek-Cyprus case with typell, in which no obvious mutation Is associated with the b5R gene, was presented. Possible molecular basis of such cases was discussed.

AB - Hereditary methemoglobinemla is an autosomal recessive disorder characterized by NADH-cytochrome bo reductase (b5R) deficiency. This disorder is classified Into two types: an erythrocyte (type I) and a generalized (type II) types. We analyzed the bSRgenes of a patient with type Üfrom a white U. K. family using PCR-related techniques, and found that the patient was a compound hétérozygote for two novel mutations, a nonsense mutation at codon 42 (TAC-TAA) and a mlssense mutation at codon 95 (CCC; Pro-CAC; His). From the allele with the nonsense mutation, the product without the catalytic portion of the enzyme Is generated. To characterize the effect of the missense mutation on the enzyme function, we compared GST-fused b5R with the GST-fused mutant enzyme expressed in Escherichia. call The mutant enzyme exhibited less catalytic activity, less thermostability and more susceptibility to trypsin than did the normal counterpart. The absorption spectrum of the mutant enzyme In the visual region differed from that of the wild type. These results suggested that this amlno acid substitution within the FAD-blnding domain of the enzyme Influences both a secondary structure and a catalytic activity of the enzyme. One Japanese case of type n was also Investigated. A novel nonesense mutation (GAG;Glu-TAG;Stop) was detected In the codon 255 of one allele, however no mutation is observed in another allele. A Greek-Cyprus case with typell, in which no obvious mutation Is associated with the b5R gene, was presented. Possible molecular basis of such cases was discussed.

UR - http://www.scopus.com/inward/record.url?scp=33748194631&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33748194631&partnerID=8YFLogxK

M3 - Article

VL - 42

JO - Journal of Human Genetics

JF - Journal of Human Genetics

SN - 1434-5161

IS - 1

ER -