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
Laboratorio de Glicobiología Humana y Diagnóstico Molecular, Centro de Investigación en Dinámica Celular, Instituto de Investigación en Ciencias Básicas y Aplicadas, Universidad Autónoma del Estado de Morelos, Cuernavaca, Mexico.
Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Mexico.
Front Genet. 2021 Sep 9;12:744884. doi: 10.3389/fgene.2021.744884. eCollection 2021.
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 , the encoding gene for the chitobiosyldiphosphodolichol beta-mannosyltransferase that participates in the formation of the dolichol-pyrophosphate-GlcNAc2Man5, a lipid-linked glycan intermediate during -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 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.
本研究报告了一名患有多系统综合征的墨西哥混血患者，该综合征包括神经受累及I型血清转铁蛋白谱。临床外显子组测序揭示了位于壳二糖二磷酸多萜醇β-甘露糖基转移酶（参与合成多萜醇焦磷酸-GlcNAc2Man5，这是N-聚糖合成过程中的一种脂质连接聚糖中间体）编码基因ALG1中的复合等位基因。鉴定出的复合等位基因分别为NM_019109.5(ALG1): c.[208 + 16_208 + 19dup; 208 + 25G > T]和NM_019109.5(ALG1): c.[208 + 16_208 + 19dup; 1312C > T]。虽然两个等位基因都携带良性变异c.208 + 16_208 + 19dup，但其中一个等位基因携带一个已知的致病变异（c.1312C > T），而另一个携带一个新的未鉴定变异（c.208 + 25G > T），该变异导致无功能的可变剪接，与良性变异一起确定了致病蛋白效应（p.N70S_S71ins9）。患者血清中存在ALG1-CDG的特征性N-连接甘露糖缺失四糖标志物（Neu5Acα2,6Galβ1,4-GlcNAcβ1,4GlcNAc）进一步支持了这一诊断。这是来自拉丁美洲的ALG1-CDG患者的首例报告。
