Distribution and genotype-phenotype correlation of GDAP1 mutations in Spain

Abstract Mutations in the GDAP1 gene can cause Charcot-Marie-Tooth disease. These mutations are quite rare in most Western countries but not so in certain regions of Spain or other Mediterranean countries. This cross-sectional retrospective multicenter study analyzed the clinical and genetic charact...

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Autores principales:	Rafael Sivera, Marina Frasquet, Vincenzo Lupo, Tania García-Sobrino, Patricia Blanco-Arias, Julio Pardo, Roberto Fernández-Torrón, Adolfo López de Munain, Celedonio Márquez-Infante, Liliana Villarreal, Pilar Carbonell, Ricard Rojas-García, Sonia Segovia, Isabel Illa, Anna Lia Frongia, Andrés Nascimento, Carlos Ortez, María del Mar García-Romero, Samuel Ignacio Pascual, Ana Lara Pelayo-Negro, José Berciano, Antonio Guerrero, Carlos Casasnovas, Ana Camacho, Jesús Esteban, María José Chumillas, Marisa Barreiro, Carmen Díaz, Francesc Palau, Juan Jesús Vílchez, Carmen Espinós, Teresa Sevilla
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0faa7f5c1e624b5b885d1c7b72e34039
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spelling	oai:doaj.org-article:0faa7f5c1e624b5b885d1c7b72e340392021-12-02T15:05:40ZDistribution and genotype-phenotype correlation of GDAP1 mutations in Spain10.1038/s41598-017-06894-62045-2322https://doaj.org/article/0faa7f5c1e624b5b885d1c7b72e340392017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-06894-6https://doaj.org/toc/2045-2322Abstract Mutations in the GDAP1 gene can cause Charcot-Marie-Tooth disease. These mutations are quite rare in most Western countries but not so in certain regions of Spain or other Mediterranean countries. This cross-sectional retrospective multicenter study analyzed the clinical and genetic characteristics of patients with GDAP1 mutations across Spain. 99 patients were identified, which were distributed across most of Spain, but especially in the Northwest and Mediterranean regions. The most common genotypes were p.R120W (in 81% of patients with autosomal dominant inheritance) and p.Q163X (in 73% of autosomal recessive patients). Patients with recessively inherited mutations had a more severe phenotype, and certain clinical features, like dysphonia or respiratory dysfunction, were exclusively detected in this group. Dominantly inherited mutations had prominent clinical variability regarding severity, including 29% of patients who were asymptomatic. There were minor clinical differences between patients harboring specific mutations but not when grouped according to localization or type of mutation. This is the largest clinical series to date of patients with GDAP1 mutations, and it contributes to define the genetic distribution and genotype-phenotype correlation in this rare form of CMT.Rafael SiveraMarina FrasquetVincenzo LupoTania García-SobrinoPatricia Blanco-AriasJulio PardoRoberto Fernández-TorrónAdolfo López de MunainCeledonio Márquez-InfanteLiliana VillarrealPilar CarbonellRicard Rojas-GarcíaSonia SegoviaIsabel IllaAnna Lia FrongiaAndrés NascimentoCarlos OrtezMaría del Mar García-RomeroSamuel Ignacio PascualAna Lara Pelayo-NegroJosé BercianoAntonio GuerreroCarlos CasasnovasAna CamachoJesús EstebanMaría José ChumillasMarisa BarreiroCarmen DíazFrancesc PalauJuan Jesús VílchezCarmen EspinósTeresa SevillaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Rafael Sivera Marina Frasquet Vincenzo Lupo Tania García-Sobrino Patricia Blanco-Arias Julio Pardo Roberto Fernández-Torrón Adolfo López de Munain Celedonio Márquez-Infante Liliana Villarreal Pilar Carbonell Ricard Rojas-García Sonia Segovia Isabel Illa Anna Lia Frongia Andrés Nascimento Carlos Ortez María del Mar García-Romero Samuel Ignacio Pascual Ana Lara Pelayo-Negro José Berciano Antonio Guerrero Carlos Casasnovas Ana Camacho Jesús Esteban María José Chumillas Marisa Barreiro Carmen Díaz Francesc Palau Juan Jesús Vílchez Carmen Espinós Teresa Sevilla Distribution and genotype-phenotype correlation of GDAP1 mutations in Spain
description	Abstract Mutations in the GDAP1 gene can cause Charcot-Marie-Tooth disease. These mutations are quite rare in most Western countries but not so in certain regions of Spain or other Mediterranean countries. This cross-sectional retrospective multicenter study analyzed the clinical and genetic characteristics of patients with GDAP1 mutations across Spain. 99 patients were identified, which were distributed across most of Spain, but especially in the Northwest and Mediterranean regions. The most common genotypes were p.R120W (in 81% of patients with autosomal dominant inheritance) and p.Q163X (in 73% of autosomal recessive patients). Patients with recessively inherited mutations had a more severe phenotype, and certain clinical features, like dysphonia or respiratory dysfunction, were exclusively detected in this group. Dominantly inherited mutations had prominent clinical variability regarding severity, including 29% of patients who were asymptomatic. There were minor clinical differences between patients harboring specific mutations but not when grouped according to localization or type of mutation. This is the largest clinical series to date of patients with GDAP1 mutations, and it contributes to define the genetic distribution and genotype-phenotype correlation in this rare form of CMT.
format	article
author	Rafael Sivera Marina Frasquet Vincenzo Lupo Tania García-Sobrino Patricia Blanco-Arias Julio Pardo Roberto Fernández-Torrón Adolfo López de Munain Celedonio Márquez-Infante Liliana Villarreal Pilar Carbonell Ricard Rojas-García Sonia Segovia Isabel Illa Anna Lia Frongia Andrés Nascimento Carlos Ortez María del Mar García-Romero Samuel Ignacio Pascual Ana Lara Pelayo-Negro José Berciano Antonio Guerrero Carlos Casasnovas Ana Camacho Jesús Esteban María José Chumillas Marisa Barreiro Carmen Díaz Francesc Palau Juan Jesús Vílchez Carmen Espinós Teresa Sevilla
author_facet	Rafael Sivera Marina Frasquet Vincenzo Lupo Tania García-Sobrino Patricia Blanco-Arias Julio Pardo Roberto Fernández-Torrón Adolfo López de Munain Celedonio Márquez-Infante Liliana Villarreal Pilar Carbonell Ricard Rojas-García Sonia Segovia Isabel Illa Anna Lia Frongia Andrés Nascimento Carlos Ortez María del Mar García-Romero Samuel Ignacio Pascual Ana Lara Pelayo-Negro José Berciano Antonio Guerrero Carlos Casasnovas Ana Camacho Jesús Esteban María José Chumillas Marisa Barreiro Carmen Díaz Francesc Palau Juan Jesús Vílchez Carmen Espinós Teresa Sevilla
author_sort	Rafael Sivera
title	Distribution and genotype-phenotype correlation of GDAP1 mutations in Spain
title_short	Distribution and genotype-phenotype correlation of GDAP1 mutations in Spain
title_full	Distribution and genotype-phenotype correlation of GDAP1 mutations in Spain
title_fullStr	Distribution and genotype-phenotype correlation of GDAP1 mutations in Spain
title_full_unstemmed	Distribution and genotype-phenotype correlation of GDAP1 mutations in Spain
title_sort	distribution and genotype-phenotype correlation of gdap1 mutations in spain
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/0faa7f5c1e624b5b885d1c7b72e34039
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Distribution and genotype-phenotype correlation of GDAP1 mutations in Spain

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