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Mutations, Clinical Findings and Survival Estimates in South American Patients with X-Linked Adrenoleukodystrophy

In this study, we analyzed the ABCD1 gene in X-linked adrenoleukodystrophy (X-ALD) patients and relatives from 38 unrelated families from South America, as well as phenotypic proportions, survival estimates, and the potential effect of geographical origin in clinical characteristics. METHODS: X- ALD...

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Autores principales: Pereira, Fernanda dos Santos, Matte, Ursula, Habekost, Clarissa Troller, de Castilhos, Raphael Machado, El Husny, Antonette Souto, Lourenço, Charles Marques, Vianna-Morgante, Angela M., Giuliani, Liane, Galera, Marcial Francis, Honjo, Rachel, Kim, Chong Ae, Politei, Juan, Vargas, Carmen Regla, Jardim, Laura Bannach
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3315551/
https://www.ncbi.nlm.nih.gov/pubmed/22479560
http://dx.doi.org/10.1371/journal.pone.0034195
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author Pereira, Fernanda dos Santos
Matte, Ursula
Habekost, Clarissa Troller
de Castilhos, Raphael Machado
El Husny, Antonette Souto
Lourenço, Charles Marques
Vianna-Morgante, Angela M.
Giuliani, Liane
Galera, Marcial Francis
Honjo, Rachel
Kim, Chong Ae
Politei, Juan
Vargas, Carmen Regla
Jardim, Laura Bannach
author_facet Pereira, Fernanda dos Santos
Matte, Ursula
Habekost, Clarissa Troller
de Castilhos, Raphael Machado
El Husny, Antonette Souto
Lourenço, Charles Marques
Vianna-Morgante, Angela M.
Giuliani, Liane
Galera, Marcial Francis
Honjo, Rachel
Kim, Chong Ae
Politei, Juan
Vargas, Carmen Regla
Jardim, Laura Bannach
author_sort Pereira, Fernanda dos Santos
collection PubMed
description In this study, we analyzed the ABCD1 gene in X-linked adrenoleukodystrophy (X-ALD) patients and relatives from 38 unrelated families from South America, as well as phenotypic proportions, survival estimates, and the potential effect of geographical origin in clinical characteristics. METHODS: X- ALD patients from Brazil, Argentina and Uruguay were invited to participate in molecular studies to determine their genetic status, characterize the mutations and improve the genetic counseling of their families. All samples were screened by SSCP analysis of PCR fragments, followed by automated DNA sequencing to establish the specific mutation in each family. Age at onset and at death, male phenotypes, genetic status of women, and the effect of family and of latitude of origin were also studied. RESULTS: We identified thirty-six different mutations (twelve novel). This population had an important allelic heterogeneity, as only p.Arg518Gln was repeatedly found (three families). Four cases carried de novo mutations. Intra-familiar phenotype variability was observed in all families. Out of 87 affected males identified, 65% had the cerebral phenotype (CALD). The mean (95% CI) ages at onset and at death of the CALD were 10.9 (9.1–12.7) and 24.7 (19.8–29.6) years. No association was found between phenotypic manifestations and latitude of origin. One index-case was a girl with CALD who carried an ABCD1 mutation, and had completely skewed X inactivation. CONCLUSIONS: This study extends the spectrum of mutations in X-ALD, confirms the high rates of de novo mutations and the absence of common mutations, and suggests a possible high frequency of cerebral forms in our population.
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spelling pubmed-33155512012-04-04 Mutations, Clinical Findings and Survival Estimates in South American Patients with X-Linked Adrenoleukodystrophy Pereira, Fernanda dos Santos Matte, Ursula Habekost, Clarissa Troller de Castilhos, Raphael Machado El Husny, Antonette Souto Lourenço, Charles Marques Vianna-Morgante, Angela M. Giuliani, Liane Galera, Marcial Francis Honjo, Rachel Kim, Chong Ae Politei, Juan Vargas, Carmen Regla Jardim, Laura Bannach PLoS One Research Article In this study, we analyzed the ABCD1 gene in X-linked adrenoleukodystrophy (X-ALD) patients and relatives from 38 unrelated families from South America, as well as phenotypic proportions, survival estimates, and the potential effect of geographical origin in clinical characteristics. METHODS: X- ALD patients from Brazil, Argentina and Uruguay were invited to participate in molecular studies to determine their genetic status, characterize the mutations and improve the genetic counseling of their families. All samples were screened by SSCP analysis of PCR fragments, followed by automated DNA sequencing to establish the specific mutation in each family. Age at onset and at death, male phenotypes, genetic status of women, and the effect of family and of latitude of origin were also studied. RESULTS: We identified thirty-six different mutations (twelve novel). This population had an important allelic heterogeneity, as only p.Arg518Gln was repeatedly found (three families). Four cases carried de novo mutations. Intra-familiar phenotype variability was observed in all families. Out of 87 affected males identified, 65% had the cerebral phenotype (CALD). The mean (95% CI) ages at onset and at death of the CALD were 10.9 (9.1–12.7) and 24.7 (19.8–29.6) years. No association was found between phenotypic manifestations and latitude of origin. One index-case was a girl with CALD who carried an ABCD1 mutation, and had completely skewed X inactivation. CONCLUSIONS: This study extends the spectrum of mutations in X-ALD, confirms the high rates of de novo mutations and the absence of common mutations, and suggests a possible high frequency of cerebral forms in our population. Public Library of Science 2012-03-29 /pmc/articles/PMC3315551/ /pubmed/22479560 http://dx.doi.org/10.1371/journal.pone.0034195 Text en Pereira et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Pereira, Fernanda dos Santos
Matte, Ursula
Habekost, Clarissa Troller
de Castilhos, Raphael Machado
El Husny, Antonette Souto
Lourenço, Charles Marques
Vianna-Morgante, Angela M.
Giuliani, Liane
Galera, Marcial Francis
Honjo, Rachel
Kim, Chong Ae
Politei, Juan
Vargas, Carmen Regla
Jardim, Laura Bannach
Mutations, Clinical Findings and Survival Estimates in South American Patients with X-Linked Adrenoleukodystrophy
title Mutations, Clinical Findings and Survival Estimates in South American Patients with X-Linked Adrenoleukodystrophy
title_full Mutations, Clinical Findings and Survival Estimates in South American Patients with X-Linked Adrenoleukodystrophy
title_fullStr Mutations, Clinical Findings and Survival Estimates in South American Patients with X-Linked Adrenoleukodystrophy
title_full_unstemmed Mutations, Clinical Findings and Survival Estimates in South American Patients with X-Linked Adrenoleukodystrophy
title_short Mutations, Clinical Findings and Survival Estimates in South American Patients with X-Linked Adrenoleukodystrophy
title_sort mutations, clinical findings and survival estimates in south american patients with x-linked adrenoleukodystrophy
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3315551/
https://www.ncbi.nlm.nih.gov/pubmed/22479560
http://dx.doi.org/10.1371/journal.pone.0034195
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