期刊
FRONTIERS IN GENETICS
卷 12, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fgene.2021.744884
关键词
CDG; splicing; metabolic; glycosylation; ALG1; mutation; tetrasaccharide
资金
- Red Tematica Glicociencia en Salud CONACyT [293399]
- Sociedad Latinoamericana de Glicobiologia
- CONACYT [957250]
- Rocket Fund and National Institutes of Health Grant [R01DK99551]
This study reports a Mexican mestizo patient with a multi-systemic syndrome involving neurological issues and a type I serum transferrin profile. Clinical exome sequencing identified complex alleles in the ALG1 gene, leading to the diagnosis of ALG1-CDG. The discovery of a previously uncharacterized variant in conjunction with a known pathogenic variant defines the pathogenic protein effect in this patient.
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 (Neu5Ac alpha 2,6Gal beta 1,4-GlcNAc beta 1,4GlcNAc) further supported this diagnosis. This is the first report of an ALG1-CDG patient from Latin America.
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