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 

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

JOURNAL=Frontiers in Genetics

VOLUME=Volume 12 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2021.744884

DOI=10.3389/fgene.2021.744884

ISSN=1664-8021

ABSTRACT=We report 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-GlcNAc(2)-Man(5) 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 define 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.