We report on a Mexican mestizo with a multisystemic syndrome including neurological involvement and a type I serum transferrin isoelectric focusing (Tf IEF) pattern. Diagnosis of PMM2-CDG was obtained by clinical exome sequencing (CES) that revealed compound heterozygous variants in PMM2, the encoding gene for the phosphomannomutase 2 (PMM2). This enzyme catalyzes the conversion of mannose-6-P to mannose-1-P required for the synthesis of GDP-Man and Dol-P-Man, donor substrates for glycosylation reactions. The identified variants were c.422G>A (R141H) and c.178G>T, the former being the most frequent PMM2 pathogenic mutation and the latter a previously uncharacterized variant restricted to the Latino population with conflicting interpretations of pathogenicity and that we here report causes leaky non-functional alternative splicing (p.V60Cfs*3).

我们报告了一名患有多系统综合征的墨西哥混血儿，包括神经系统受累和 I 型血清转铁蛋白等电聚焦 (Tf IEF) 模式。PMM2-CDG 的诊断是通过临床外显子组测序 (CES) 获得的，该测序揭示了PMM2（磷酸甘露糖变位酶 2 (PMM2) 的编码基因）中的复合杂合变体。该酶催化甘露糖-6-P 转化为合成 GDP-Man 和 Dol-P-Man（糖基化反应的供体底物）所需的甘露糖-1-P。确定的变体是 c.422G>A (R141H) 和 c.178G>T，前者是最常见的PMM2 致病突变，后者是以前未表征的变异，仅限于拉丁裔人群，对致病性的解释相互矛盾，我们在此报告导致泄漏的非功能性选择性剪接 (p.V60Cfs*3)。