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=12 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=

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.