| Autor: |
Sonal, Mahajan, Bobby George, Ng, Lama, AlAbdi, Paul Daniel James, Earnest, Paulina, Sosicka, Nisha, Patel, Rana, Helaby, Firdous, Abdulwahab, Miao, He, Fowzan S, Alkuraya, Hudson H, Freeze |
| Rok vydání: |
2022 |
| Zdroj: |
Journal of medical genetics. |
| ISSN: |
1468-6244 |
| Popis: |
Enzymes of the Golgi implicated in N-glycan processing are critical for brain development, and defects in many are defined as congenital disorders of glycosylation (CDG). Involvement of the Golgi mannosidase, MAN2A2 has not been identified previously as causing glycosylation defects.Exome sequencing of affected individuals was performed with Sanger sequencing of theWe identified a multiplex consanguineous family with a homozygous truncating variant p.Val1101Ter in MAN2A2. Lymphoblasts from two affected brothers carrying the same truncating variant showed decreases in complex N-glycans and accumulation of hybrid N-glycans. On testing of this variant in the developed complementation assay, we see the complete lack of complex N-glycans.Our findings show that pathogenic variants in MAN2A2 cause a novel autosomal recessive CDG with neurological involvement and facial dysmorphism. Here, we also present the development of a cell-based complementation assay to assess the pathogenicity of MAN2A2 variants, which can also be extended to MAN2A1 variants for future diagnosis. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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