Methionine adenosyltransferase I/III deficiency: two Korean compound heterozygous siblings with a novel mutation

Two Korean sisters, one detected during neonatal screening, the other ascertained at age 3 years during family screening, have persistent hypermethioninaemia without elevation of plasma tyrosine or severe liver disease. Plasma total homocysteine (tHcy) is mildly elevated, but not so markedly as to e...

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Autores: Kim, S.Z. (S. Z.)|||/items/9ea6efda-0f79-497c-b90b-7c2aa7c4af50, Santamaria, E. (Enrique)|||/items/fc2c70d6-973c-4d67-8185-6c56a59477c8, Jeong, T.E. (T. E.)|||/items/12a7a1fb-3be4-49de-80c0-6add84596030, Levy, H.L. (H.L.)|||/items/47c98f41-700f-437e-abcd-9522840668fb, Mato, J.M. (José María)|||/items/302dc624-b0d3-4703-90cf-1a97690ebc79, Corrales, F.J. (Fernando José)|||/items/96b34843-1185-4837-be4b-d1d63e688ec2, Mudd, S.H. (S. Harvey)|||/items/9a56a577-66d3-40ec-836e-ee86a7498af8
Tipo de recurso: artículo
Fecha de publicación:2002
País:España
Institución:Universidad de Navarra
Repositorio:Dadun. Depósito Académico Digital de la Universidad de Navarra
Idioma:inglés
OAI Identifier:oai:dadun.unav.edu:10171/21488
Acceso en línea:https://hdl.handle.net/10171/21488
Access Level:acceso abierto
Palabra clave:Methionine Adenosyltransferase/deficiency
Mutation/genetics
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spelling Methionine adenosyltransferase I/III deficiency: two Korean compound heterozygous siblings with a novel mutationKim, S.Z. (S. Z.)|||/items/9ea6efda-0f79-497c-b90b-7c2aa7c4af50Santamaria, E. (Enrique)|||/items/fc2c70d6-973c-4d67-8185-6c56a59477c8Jeong, T.E. (T. E.)|||/items/12a7a1fb-3be4-49de-80c0-6add84596030Levy, H.L. (H.L.)|||/items/47c98f41-700f-437e-abcd-9522840668fbMato, J.M. (José María)|||/items/302dc624-b0d3-4703-90cf-1a97690ebc79Corrales, F.J. (Fernando José)|||/items/96b34843-1185-4837-be4b-d1d63e688ec2Mudd, S.H. (S. Harvey)|||/items/9a56a577-66d3-40ec-836e-ee86a7498af8Methionine Adenosyltransferase/deficiencyMutation/geneticsTwo Korean sisters, one detected during neonatal screening, the other ascertained at age 3 years during family screening, have persistent hypermethioninaemia without elevation of plasma tyrosine or severe liver disease. Plasma total homocysteine (tHcy) is mildly elevated, but not so markedly as to establish a diagnosis of homocystinuria due to cystathionine beta-synthase (CBS) deficiency. CBS deficiency was ruled out by the presence of slightly elevated concentrations of plasma cystathionine. Although the plasma concentrations of methionine were markedly elevated, plasma S-adenosylmethionine (AdoMet) was not. This pattern of metabolic abnormalities suggested that the patients have deficient activity of methionine adenosyltransferase (MAT) in their livers (MAT I/III deficiency). Molecular genetic studies demonstrate that each patient is a compound heterozygote for two mutations in MAT1A, the gene that encodes the catalytic subunit that composes MAT I and MAT III: a previously known inactivating G378S point mutation, and a novel W387X truncating mutation. W387X mutant protein, expressed in E. coli and purified, has about 75% of wild-type activity. Negative subunit interaction between the mutant subunits is suggested to explain the hypermethioninaemia of these sisters. They have had normal growth and development and have no mental retardation, neurological abnormalities, or other clinical problems. They are the first individuals of Korean descent proven to have MAT I/III deficiency.Springer VerlagDadun. Depósito Académico Digital Universidad de Navarra20122012-04-0220022002-01-0120022002-01-01journal articlehttp://purl.org/coar/resource_type/c_6501info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/10171/21488reponame:Dadun. Depósito Académico Digital de la Universidad de Navarrainstname:Universidad de NavarraInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:dadun.unav.edu:10171/214882026-06-21T12:47:57Z
dc.title.none.fl_str_mv Methionine adenosyltransferase I/III deficiency: two Korean compound heterozygous siblings with a novel mutation
title Methionine adenosyltransferase I/III deficiency: two Korean compound heterozygous siblings with a novel mutation
spellingShingle Methionine adenosyltransferase I/III deficiency: two Korean compound heterozygous siblings with a novel mutation
Kim, S.Z. (S. Z.)|||/items/9ea6efda-0f79-497c-b90b-7c2aa7c4af50
Methionine Adenosyltransferase/deficiency
Mutation/genetics
title_short Methionine adenosyltransferase I/III deficiency: two Korean compound heterozygous siblings with a novel mutation
title_full Methionine adenosyltransferase I/III deficiency: two Korean compound heterozygous siblings with a novel mutation
title_fullStr Methionine adenosyltransferase I/III deficiency: two Korean compound heterozygous siblings with a novel mutation
title_full_unstemmed Methionine adenosyltransferase I/III deficiency: two Korean compound heterozygous siblings with a novel mutation
title_sort Methionine adenosyltransferase I/III deficiency: two Korean compound heterozygous siblings with a novel mutation
dc.creator.none.fl_str_mv Kim, S.Z. (S. Z.)|||/items/9ea6efda-0f79-497c-b90b-7c2aa7c4af50
Santamaria, E. (Enrique)|||/items/fc2c70d6-973c-4d67-8185-6c56a59477c8
Jeong, T.E. (T. E.)|||/items/12a7a1fb-3be4-49de-80c0-6add84596030
Levy, H.L. (H.L.)|||/items/47c98f41-700f-437e-abcd-9522840668fb
Mato, J.M. (José María)|||/items/302dc624-b0d3-4703-90cf-1a97690ebc79
Corrales, F.J. (Fernando José)|||/items/96b34843-1185-4837-be4b-d1d63e688ec2
Mudd, S.H. (S. Harvey)|||/items/9a56a577-66d3-40ec-836e-ee86a7498af8
author Kim, S.Z. (S. Z.)|||/items/9ea6efda-0f79-497c-b90b-7c2aa7c4af50
author_facet Kim, S.Z. (S. Z.)|||/items/9ea6efda-0f79-497c-b90b-7c2aa7c4af50
Santamaria, E. (Enrique)|||/items/fc2c70d6-973c-4d67-8185-6c56a59477c8
Jeong, T.E. (T. E.)|||/items/12a7a1fb-3be4-49de-80c0-6add84596030
Levy, H.L. (H.L.)|||/items/47c98f41-700f-437e-abcd-9522840668fb
Mato, J.M. (José María)|||/items/302dc624-b0d3-4703-90cf-1a97690ebc79
Corrales, F.J. (Fernando José)|||/items/96b34843-1185-4837-be4b-d1d63e688ec2
Mudd, S.H. (S. Harvey)|||/items/9a56a577-66d3-40ec-836e-ee86a7498af8
author_role author
author2 Santamaria, E. (Enrique)|||/items/fc2c70d6-973c-4d67-8185-6c56a59477c8
Jeong, T.E. (T. E.)|||/items/12a7a1fb-3be4-49de-80c0-6add84596030
Levy, H.L. (H.L.)|||/items/47c98f41-700f-437e-abcd-9522840668fb
Mato, J.M. (José María)|||/items/302dc624-b0d3-4703-90cf-1a97690ebc79
Corrales, F.J. (Fernando José)|||/items/96b34843-1185-4837-be4b-d1d63e688ec2
Mudd, S.H. (S. Harvey)|||/items/9a56a577-66d3-40ec-836e-ee86a7498af8
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Dadun. Depósito Académico Digital Universidad de Navarra
dc.subject.none.fl_str_mv Methionine Adenosyltransferase/deficiency
Mutation/genetics
topic Methionine Adenosyltransferase/deficiency
Mutation/genetics
description Two Korean sisters, one detected during neonatal screening, the other ascertained at age 3 years during family screening, have persistent hypermethioninaemia without elevation of plasma tyrosine or severe liver disease. Plasma total homocysteine (tHcy) is mildly elevated, but not so markedly as to establish a diagnosis of homocystinuria due to cystathionine beta-synthase (CBS) deficiency. CBS deficiency was ruled out by the presence of slightly elevated concentrations of plasma cystathionine. Although the plasma concentrations of methionine were markedly elevated, plasma S-adenosylmethionine (AdoMet) was not. This pattern of metabolic abnormalities suggested that the patients have deficient activity of methionine adenosyltransferase (MAT) in their livers (MAT I/III deficiency). Molecular genetic studies demonstrate that each patient is a compound heterozygote for two mutations in MAT1A, the gene that encodes the catalytic subunit that composes MAT I and MAT III: a previously known inactivating G378S point mutation, and a novel W387X truncating mutation. W387X mutant protein, expressed in E. coli and purified, has about 75% of wild-type activity. Negative subunit interaction between the mutant subunits is suggested to explain the hypermethioninaemia of these sisters. They have had normal growth and development and have no mental retardation, neurological abnormalities, or other clinical problems. They are the first individuals of Korean descent proven to have MAT I/III deficiency.
publishDate 2002
dc.date.none.fl_str_mv 2002
2002-01-01
2002
2002-01-01
2012
2012-04-02
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/10171/21488
url https://hdl.handle.net/10171/21488
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Springer Verlag
publisher.none.fl_str_mv Springer Verlag
dc.source.none.fl_str_mv reponame:Dadun. Depósito Académico Digital de la Universidad de Navarra
instname:Universidad de Navarra
instname_str Universidad de Navarra
reponame_str Dadun. Depósito Académico Digital de la Universidad de Navarra
collection Dadun. Depósito Académico Digital de la Universidad de Navarra
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.300719

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