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ALG1-CDG Caused by Non-functional Alternative Splicing Involving a Novel Pathogenic Complex Allele

This study reports on a Mexican mestizo patient with a multi-systemic syndrome including neurological involvement and a type I serum transferrin profile. Clinical exome sequencing revealed complex alleles in ALG1, the encoding gene for the chitobiosyldiphosphodolichol beta-mannosyltransferase that p...

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Autores principales: González-Domínguez, Carlos Alberto, Fiesco-Roa, Moisés O., Gómez-Carmona, Samuel, Kleinert-Altamirano, Anke Paula Ingrid, He, Miao, Daniel, Earnest James Paul, Raymond, Kimiyo M., Abreu-González, Melania, Manrique-Hernández, Sandra, González-Jaimes, Ana, Salinas-Marín, Roberta, Molina-Garay, Carolina, Carrillo-Sánchez, Karol, Flores-Lagunes, Luis Leonardo, Jiménez-Olivares, Marco, Muñoz-Rivas, Anallely, Cruz-Muñoz, Mario E., Ruíz-García, Matilde, Freeze, Hudson H., Mora-Montes, Héctor M., Alaez-Verson, Carmen, Martínez-Duncker, Iván
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8458739/
https://www.ncbi.nlm.nih.gov/pubmed/34567092
http://dx.doi.org/10.3389/fgene.2021.744884
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author González-Domínguez, Carlos Alberto
Fiesco-Roa, Moisés O.
Gómez-Carmona, Samuel
Kleinert-Altamirano, Anke Paula Ingrid
He, Miao
Daniel, Earnest James Paul
Raymond, Kimiyo M.
Abreu-González, Melania
Manrique-Hernández, Sandra
González-Jaimes, Ana
Salinas-Marín, Roberta
Molina-Garay, Carolina
Carrillo-Sánchez, Karol
Flores-Lagunes, Luis Leonardo
Jiménez-Olivares, Marco
Muñoz-Rivas, Anallely
Cruz-Muñoz, Mario E.
Ruíz-García, Matilde
Freeze, Hudson H.
Mora-Montes, Héctor M.
Alaez-Verson, Carmen
Martínez-Duncker, Iván
author_facet González-Domínguez, Carlos Alberto
Fiesco-Roa, Moisés O.
Gómez-Carmona, Samuel
Kleinert-Altamirano, Anke Paula Ingrid
He, Miao
Daniel, Earnest James Paul
Raymond, Kimiyo M.
Abreu-González, Melania
Manrique-Hernández, Sandra
González-Jaimes, Ana
Salinas-Marín, Roberta
Molina-Garay, Carolina
Carrillo-Sánchez, Karol
Flores-Lagunes, Luis Leonardo
Jiménez-Olivares, Marco
Muñoz-Rivas, Anallely
Cruz-Muñoz, Mario E.
Ruíz-García, Matilde
Freeze, Hudson H.
Mora-Montes, Héctor M.
Alaez-Verson, Carmen
Martínez-Duncker, Iván
author_sort González-Domínguez, Carlos Alberto
collection PubMed
description This study reports on a Mexican mestizo patient with a multi-systemic syndrome including neurological involvement and a type I serum transferrin profile. Clinical exome sequencing revealed complex alleles in ALG1, the encoding gene for the chitobiosyldiphosphodolichol beta-mannosyltransferase that participates in the formation of the dolichol-pyrophosphate-GlcNAc2Man5, a lipid-linked glycan intermediate during N-glycan synthesis. The identified complex alleles were NM_019109.5(ALG1): c.[208 + 16_208 + 19dup; 208 + 25G > T] and NM_019109.5(ALG1): c.[208 + 16_208 + 19dup; 1312C > T]. Although both alleles carried the benign variant c.208 + 16_208 + 19dup, one allele carried a known ALG1 pathogenic variant (c.1312C > T), while the other carried a new uncharacterized variant (c.208 + 25G > T) causing non-functional alternative splicing that, in conjunction with the benign variant, defines the pathogenic protein effect (p.N70S_S71ins9). The presence in the patient’s serum of the pathognomonic N-linked mannose-deprived tetrasaccharide marker for ALG1-CDG (Neu5Acα2,6Galβ1,4-GlcNAcβ1,4GlcNAc) further supported this diagnosis. This is the first report of an ALG1-CDG patient from Latin America.
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spelling pubmed-84587392021-09-24 ALG1-CDG Caused by Non-functional Alternative Splicing Involving a Novel Pathogenic Complex Allele González-Domínguez, Carlos Alberto Fiesco-Roa, Moisés O. Gómez-Carmona, Samuel Kleinert-Altamirano, Anke Paula Ingrid He, Miao Daniel, Earnest James Paul Raymond, Kimiyo M. Abreu-González, Melania Manrique-Hernández, Sandra González-Jaimes, Ana Salinas-Marín, Roberta Molina-Garay, Carolina Carrillo-Sánchez, Karol Flores-Lagunes, Luis Leonardo Jiménez-Olivares, Marco Muñoz-Rivas, Anallely Cruz-Muñoz, Mario E. Ruíz-García, Matilde Freeze, Hudson H. Mora-Montes, Héctor M. Alaez-Verson, Carmen Martínez-Duncker, Iván Front Genet Genetics This study reports on a Mexican mestizo patient with a multi-systemic syndrome including neurological involvement and a type I serum transferrin profile. Clinical exome sequencing revealed complex alleles in ALG1, the encoding gene for the chitobiosyldiphosphodolichol beta-mannosyltransferase that participates in the formation of the dolichol-pyrophosphate-GlcNAc2Man5, a lipid-linked glycan intermediate during N-glycan synthesis. The identified complex alleles were NM_019109.5(ALG1): c.[208 + 16_208 + 19dup; 208 + 25G > T] and NM_019109.5(ALG1): c.[208 + 16_208 + 19dup; 1312C > T]. Although both alleles carried the benign variant c.208 + 16_208 + 19dup, one allele carried a known ALG1 pathogenic variant (c.1312C > T), while the other carried a new uncharacterized variant (c.208 + 25G > T) causing non-functional alternative splicing that, in conjunction with the benign variant, defines the pathogenic protein effect (p.N70S_S71ins9). The presence in the patient’s serum of the pathognomonic N-linked mannose-deprived tetrasaccharide marker for ALG1-CDG (Neu5Acα2,6Galβ1,4-GlcNAcβ1,4GlcNAc) further supported this diagnosis. This is the first report of an ALG1-CDG patient from Latin America. Frontiers Media S.A. 2021-09-09 /pmc/articles/PMC8458739/ /pubmed/34567092 http://dx.doi.org/10.3389/fgene.2021.744884 Text en Copyright © 2021 González-Domínguez, Fiesco-Roa, Gómez-Carmona, Kleinert-Altamirano, He, Daniel, Raymond, Abreu-González, Manrique-Hernández, González-Jaimes, Salinas-Marín, Molina-Garay, Carrillo-Sánchez, Flores-Lagunes, Jiménez-Olivares, Muñoz-Rivas, Cruz-Muñoz, Ruíz-García, Freeze, Mora-Montes, Alaez-Verson and Martínez-Duncker. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Genetics
González-Domínguez, Carlos Alberto
Fiesco-Roa, Moisés O.
Gómez-Carmona, Samuel
Kleinert-Altamirano, Anke Paula Ingrid
He, Miao
Daniel, Earnest James Paul
Raymond, Kimiyo M.
Abreu-González, Melania
Manrique-Hernández, Sandra
González-Jaimes, Ana
Salinas-Marín, Roberta
Molina-Garay, Carolina
Carrillo-Sánchez, Karol
Flores-Lagunes, Luis Leonardo
Jiménez-Olivares, Marco
Muñoz-Rivas, Anallely
Cruz-Muñoz, Mario E.
Ruíz-García, Matilde
Freeze, Hudson H.
Mora-Montes, Héctor M.
Alaez-Verson, Carmen
Martínez-Duncker, Iván
ALG1-CDG Caused by Non-functional Alternative Splicing Involving a Novel Pathogenic Complex Allele
title ALG1-CDG Caused by Non-functional Alternative Splicing Involving a Novel Pathogenic Complex Allele
title_full ALG1-CDG Caused by Non-functional Alternative Splicing Involving a Novel Pathogenic Complex Allele
title_fullStr ALG1-CDG Caused by Non-functional Alternative Splicing Involving a Novel Pathogenic Complex Allele
title_full_unstemmed ALG1-CDG Caused by Non-functional Alternative Splicing Involving a Novel Pathogenic Complex Allele
title_short ALG1-CDG Caused by Non-functional Alternative Splicing Involving a Novel Pathogenic Complex Allele
title_sort alg1-cdg caused by non-functional alternative splicing involving a novel pathogenic complex allele
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8458739/
https://www.ncbi.nlm.nih.gov/pubmed/34567092
http://dx.doi.org/10.3389/fgene.2021.744884
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