Phenylalanine Hydroxylase (PAH) Genotyping in PKU Argentine Patients

Autores
Enacán, Rosa E.; Miñana, Mariana Nuñez; Fernandez, Luis; Valle, María Gabriela; Salerno, Mercedes; Fraga, Claudia I.; Santos Simarro, Fernando; Prieto, Laura; Lapunzina, Pablo; Specola, Norma; Chiesa, Ana Elena
Año de publicación
2019
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Phenylketonuria (PKU, OMIM 261600) is predominantly caused by mutations in the PAH gene. One hundred and three Argentine PKU patients were studied by Sanger sequencing; 101 were completely characterized (90.3% were compound heterozygotes). Fifty-four different pathogenic variants were identified. Mutations were distributed all along the PAH gene but concentrated in exon 7 (26%), 12 (12%), 11 (10%), and 6 (10%). 77% were missense, and 77% affected the enzyme catalytic domain, nine mutations accounted for 57% of 179 studied alleles: p.Arg261Gln (Allele frequency(AF):10.6%), c.1066-11G>A (AF:9,5%), p.Arg408Trp (AF:8,3%), p.Tyr414Cys (AF:5,5%), p.Ala403Val, p.Val388Met, and p.Arg158Gln (AF: 5% each), p.Leu48Ser, and p.Ile65Thr (AF:4% each). The predicted phenotype was assigned by Guldberg´s arbitrary value (AV) and compared with the clinical phenotype based in tolerance to Phe intake. 29.1% (n:30) were hyperphenylalaninemias, 18.5% (n:19) mild-PKU, 27.2% (n:28) moderate-PKU and 25.2 % (n:26) classical-PKU. Genotype/phenotype correlation was statistically significant (p<0.001) Overall concordance was 62,5%: 93.3% in hyperphenylalaninemia, 64.7% in mild-PKU and 65.4% in classical patients. The moderate-PKU showed a weak concordance (17%) with milder AV prediction than clinical assessment. 74% of discordant moderate patients harbored p.Arg261Gln, and p.Val388Met. Our cohort is highly heterogeneous, with predominant Mediterranean influence (mainly Spanish), but with differences with other Latin-American countries.
Fil: Enacán, Rosa E.. Fundacion de Endocrinologia Infantil.; Argentina
Fil: Miñana, Mariana Nuñez. Provincia de Buenos Aires. Ministerio de Salud. Hospital de Niños "Sor María Ludovica" de La Plata; Argentina
Fil: Fernandez, Luis. Universidad Autónoma de Madrid; España
Fil: Valle, María Gabriela. Fundacion de Endocrinologia Infantil.; Argentina
Fil: Salerno, Mercedes. Provincia de Buenos Aires. Ministerio de Salud. Hospital de Niños "Sor María Ludovica" de La Plata; Argentina
Fil: Fraga, Claudia I.. Fundacion de Endocrinologia Infantil.; Argentina
Fil: Santos Simarro, Fernando. Universidad Autónoma de Madrid; España
Fil: Prieto, Laura. Fundacion de Endocrinologia Infantil.; Argentina
Fil: Lapunzina, Pablo. Universidad Autónoma de Madrid; España
Fil: Specola, Norma. Provincia de Buenos Aires. Ministerio de Salud. Hospital de Niños "Sor María Ludovica" de La Plata; Argentina
Fil: Chiesa, Ana Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina. Fundacion de Endocrinologia Infantil.; Argentina
Materia
PKU
GENOTYPING
PHENYLALAINE HIDROXILASE
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/152928
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/152928
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Phenylalanine Hydroxylase (PAH) Genotyping in PKU Argentine PatientsEnacán, Rosa E.Miñana, Mariana NuñezFernandez, LuisValle, María GabrielaSalerno, MercedesFraga, Claudia I.Santos Simarro, FernandoPrieto, LauraLapunzina, PabloSpecola, NormaChiesa, Ana ElenaPKUGENOTYPINGPHENYLALAINE HIDROXILASEhttps://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3Phenylketonuria (PKU, OMIM 261600) is predominantly caused by mutations in the PAH gene. One hundred and three Argentine PKU patients were studied by Sanger sequencing; 101 were completely characterized (90.3% were compound heterozygotes). Fifty-four different pathogenic variants were identified. Mutations were distributed all along the PAH gene but concentrated in exon 7 (26%), 12 (12%), 11 (10%), and 6 (10%). 77% were missense, and 77% affected the enzyme catalytic domain, nine mutations accounted for 57% of 179 studied alleles: p.Arg261Gln (Allele frequency(AF):10.6%), c.1066-11G>A (AF:9,5%), p.Arg408Trp (AF:8,3%), p.Tyr414Cys (AF:5,5%), p.Ala403Val, p.Val388Met, and p.Arg158Gln (AF: 5% each), p.Leu48Ser, and p.Ile65Thr (AF:4% each). The predicted phenotype was assigned by Guldberg´s arbitrary value (AV) and compared with the clinical phenotype based in tolerance to Phe intake. 29.1% (n:30) were hyperphenylalaninemias, 18.5% (n:19) mild-PKU, 27.2% (n:28) moderate-PKU and 25.2 % (n:26) classical-PKU. Genotype/phenotype correlation was statistically significant (p<0.001) Overall concordance was 62,5%: 93.3% in hyperphenylalaninemia, 64.7% in mild-PKU and 65.4% in classical patients. The moderate-PKU showed a weak concordance (17%) with milder AV prediction than clinical assessment. 74% of discordant moderate patients harbored p.Arg261Gln, and p.Val388Met. Our cohort is highly heterogeneous, with predominant Mediterranean influence (mainly Spanish), but with differences with other Latin-American countries.Fil: Enacán, Rosa E.. Fundacion de Endocrinologia Infantil.; ArgentinaFil: Miñana, Mariana Nuñez. Provincia de Buenos Aires. Ministerio de Salud. Hospital de Niños "Sor María Ludovica" de La Plata; ArgentinaFil: Fernandez, Luis. Universidad Autónoma de Madrid; EspañaFil: Valle, María Gabriela. Fundacion de Endocrinologia Infantil.; ArgentinaFil: Salerno, Mercedes. Provincia de Buenos Aires. Ministerio de Salud. Hospital de Niños "Sor María Ludovica" de La Plata; ArgentinaFil: Fraga, Claudia I.. Fundacion de Endocrinologia Infantil.; ArgentinaFil: Santos Simarro, Fernando. Universidad Autónoma de Madrid; EspañaFil: Prieto, Laura. Fundacion de Endocrinologia Infantil.; ArgentinaFil: Lapunzina, Pablo. Universidad Autónoma de Madrid; EspañaFil: Specola, Norma. Provincia de Buenos Aires. Ministerio de Salud. Hospital de Niños "Sor María Ludovica" de La Plata; ArgentinaFil: Chiesa, Ana Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina. Fundacion de Endocrinologia Infantil.; ArgentinaSage Publications Ltd2019-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/152928Enacán, Rosa E.; Miñana, Mariana Nuñez; Fernandez, Luis; Valle, María Gabriela; Salerno, Mercedes; et al.; Phenylalanine Hydroxylase (PAH) Genotyping in PKU Argentine Patients; Sage Publications Ltd; Journal of Inborn Errors of Metabolism and Screening; 7; e20190012; 12-2019; 1-82326-4594CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://www.scielo.br/scielo.php?script=sci_arttext&pid=S2326-45942019000100309&tlng=eninfo:eu-repo/semantics/altIdentifier/doi/10.1590/2326-4594-jiems-2019-0012info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:03:53Zoai:ri.conicet.gov.ar:11336/152928instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:03:53.91CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Phenylalanine Hydroxylase (PAH) Genotyping in PKU Argentine Patients
title Phenylalanine Hydroxylase (PAH) Genotyping in PKU Argentine Patients
spellingShingle Phenylalanine Hydroxylase (PAH) Genotyping in PKU Argentine Patients
Enacán, Rosa E.
PKU
GENOTYPING
PHENYLALAINE HIDROXILASE
title_short Phenylalanine Hydroxylase (PAH) Genotyping in PKU Argentine Patients
title_full Phenylalanine Hydroxylase (PAH) Genotyping in PKU Argentine Patients
title_fullStr Phenylalanine Hydroxylase (PAH) Genotyping in PKU Argentine Patients
title_full_unstemmed Phenylalanine Hydroxylase (PAH) Genotyping in PKU Argentine Patients
title_sort Phenylalanine Hydroxylase (PAH) Genotyping in PKU Argentine Patients
dc.creator.none.fl_str_mv Enacán, Rosa E.
Miñana, Mariana Nuñez
Fernandez, Luis
Valle, María Gabriela
Salerno, Mercedes
Fraga, Claudia I.
Santos Simarro, Fernando
Prieto, Laura
Lapunzina, Pablo
Specola, Norma
Chiesa, Ana Elena
author Enacán, Rosa E.
author_facet Enacán, Rosa E.
Miñana, Mariana Nuñez
Fernandez, Luis
Valle, María Gabriela
Salerno, Mercedes
Fraga, Claudia I.
Santos Simarro, Fernando
Prieto, Laura
Lapunzina, Pablo
Specola, Norma
Chiesa, Ana Elena
author_role author
author2 Miñana, Mariana Nuñez
Fernandez, Luis
Valle, María Gabriela
Salerno, Mercedes
Fraga, Claudia I.
Santos Simarro, Fernando
Prieto, Laura
Lapunzina, Pablo
Specola, Norma
Chiesa, Ana Elena
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv PKU
GENOTYPING
PHENYLALAINE HIDROXILASE
topic PKU
GENOTYPING
PHENYLALAINE HIDROXILASE
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.2
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Phenylketonuria (PKU, OMIM 261600) is predominantly caused by mutations in the PAH gene. One hundred and three Argentine PKU patients were studied by Sanger sequencing; 101 were completely characterized (90.3% were compound heterozygotes). Fifty-four different pathogenic variants were identified. Mutations were distributed all along the PAH gene but concentrated in exon 7 (26%), 12 (12%), 11 (10%), and 6 (10%). 77% were missense, and 77% affected the enzyme catalytic domain, nine mutations accounted for 57% of 179 studied alleles: p.Arg261Gln (Allele frequency(AF):10.6%), c.1066-11G>A (AF:9,5%), p.Arg408Trp (AF:8,3%), p.Tyr414Cys (AF:5,5%), p.Ala403Val, p.Val388Met, and p.Arg158Gln (AF: 5% each), p.Leu48Ser, and p.Ile65Thr (AF:4% each). The predicted phenotype was assigned by Guldberg´s arbitrary value (AV) and compared with the clinical phenotype based in tolerance to Phe intake. 29.1% (n:30) were hyperphenylalaninemias, 18.5% (n:19) mild-PKU, 27.2% (n:28) moderate-PKU and 25.2 % (n:26) classical-PKU. Genotype/phenotype correlation was statistically significant (p<0.001) Overall concordance was 62,5%: 93.3% in hyperphenylalaninemia, 64.7% in mild-PKU and 65.4% in classical patients. The moderate-PKU showed a weak concordance (17%) with milder AV prediction than clinical assessment. 74% of discordant moderate patients harbored p.Arg261Gln, and p.Val388Met. Our cohort is highly heterogeneous, with predominant Mediterranean influence (mainly Spanish), but with differences with other Latin-American countries.
Fil: Enacán, Rosa E.. Fundacion de Endocrinologia Infantil.; Argentina
Fil: Miñana, Mariana Nuñez. Provincia de Buenos Aires. Ministerio de Salud. Hospital de Niños "Sor María Ludovica" de La Plata; Argentina
Fil: Fernandez, Luis. Universidad Autónoma de Madrid; España
Fil: Valle, María Gabriela. Fundacion de Endocrinologia Infantil.; Argentina
Fil: Salerno, Mercedes. Provincia de Buenos Aires. Ministerio de Salud. Hospital de Niños "Sor María Ludovica" de La Plata; Argentina
Fil: Fraga, Claudia I.. Fundacion de Endocrinologia Infantil.; Argentina
Fil: Santos Simarro, Fernando. Universidad Autónoma de Madrid; España
Fil: Prieto, Laura. Fundacion de Endocrinologia Infantil.; Argentina
Fil: Lapunzina, Pablo. Universidad Autónoma de Madrid; España
Fil: Specola, Norma. Provincia de Buenos Aires. Ministerio de Salud. Hospital de Niños "Sor María Ludovica" de La Plata; Argentina
Fil: Chiesa, Ana Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina. Fundacion de Endocrinologia Infantil.; Argentina
description Phenylketonuria (PKU, OMIM 261600) is predominantly caused by mutations in the PAH gene. One hundred and three Argentine PKU patients were studied by Sanger sequencing; 101 were completely characterized (90.3% were compound heterozygotes). Fifty-four different pathogenic variants were identified. Mutations were distributed all along the PAH gene but concentrated in exon 7 (26%), 12 (12%), 11 (10%), and 6 (10%). 77% were missense, and 77% affected the enzyme catalytic domain, nine mutations accounted for 57% of 179 studied alleles: p.Arg261Gln (Allele frequency(AF):10.6%), c.1066-11G>A (AF:9,5%), p.Arg408Trp (AF:8,3%), p.Tyr414Cys (AF:5,5%), p.Ala403Val, p.Val388Met, and p.Arg158Gln (AF: 5% each), p.Leu48Ser, and p.Ile65Thr (AF:4% each). The predicted phenotype was assigned by Guldberg´s arbitrary value (AV) and compared with the clinical phenotype based in tolerance to Phe intake. 29.1% (n:30) were hyperphenylalaninemias, 18.5% (n:19) mild-PKU, 27.2% (n:28) moderate-PKU and 25.2 % (n:26) classical-PKU. Genotype/phenotype correlation was statistically significant (p<0.001) Overall concordance was 62,5%: 93.3% in hyperphenylalaninemia, 64.7% in mild-PKU and 65.4% in classical patients. The moderate-PKU showed a weak concordance (17%) with milder AV prediction than clinical assessment. 74% of discordant moderate patients harbored p.Arg261Gln, and p.Val388Met. Our cohort is highly heterogeneous, with predominant Mediterranean influence (mainly Spanish), but with differences with other Latin-American countries.
publishDate 2019
dc.date.none.fl_str_mv 2019-12
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/152928
Enacán, Rosa E.; Miñana, Mariana Nuñez; Fernandez, Luis; Valle, María Gabriela; Salerno, Mercedes; et al.; Phenylalanine Hydroxylase (PAH) Genotyping in PKU Argentine Patients; Sage Publications Ltd; Journal of Inborn Errors of Metabolism and Screening; 7; e20190012; 12-2019; 1-8
2326-4594
CONICET Digital
CONICET
url http://hdl.handle.net/11336/152928
identifier_str_mv Enacán, Rosa E.; Miñana, Mariana Nuñez; Fernandez, Luis; Valle, María Gabriela; Salerno, Mercedes; et al.; Phenylalanine Hydroxylase (PAH) Genotyping in PKU Argentine Patients; Sage Publications Ltd; Journal of Inborn Errors of Metabolism and Screening; 7; e20190012; 12-2019; 1-8
2326-4594
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.scielo.br/scielo.php?script=sci_arttext&pid=S2326-45942019000100309&tlng=en
info:eu-repo/semantics/altIdentifier/doi/10.1590/2326-4594-jiems-2019-0012
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Sage Publications Ltd
publisher.none.fl_str_mv Sage Publications Ltd
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.070432

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