MAN2B2 and Congenital Disorder of Glycosylation

This summary describes the association between MAN2B2 and congenital disorder of glycosylation based on rare case reports and functional assessments. Two independent studies reported compound heterozygous variants in MAN2B2 in patients with clinical features of CDG, including dysmorphic facial features, cleft palate, hypospadias, seizures, dehydration, and abnormal lymphocyte morphology (PMID:35637269, PMID:38622837). In one report the proband was found to carry the variant c.2368G>A (p.Glu790Lys) while a second study identified two variants, c.384G>T (p.Gln128His) and c.926T>A (p.Ile309Asn), segregating with the disease under an autosomal recessive inheritance pattern. Functional studies employing MALDI‑TOF MS and LC‑MS/MS analyses revealed disrupted N‑linked glycosylation that is consistent with the clinical manifestations, thereby supporting the pathogenicity of the identified variants (PMID:35637269).

Despite the limited number of reported probands, the experimental evidence demonstrates a biologically plausible mechanism by which MAN2B2 variants may lead to a glycosylation defect and ensuing multiorgan involvement. The integration of genetic findings with functional data provides a basis for considering this association in diagnostic decision‑making, although further studies are needed to fully elucidate the clinical spectrum of MAN2B2‑related CDG. Key take‑home sentence: While current evidence is limited, the reported variants in MAN2B2, supported by functional disruption of glycosylation, underscore its potential clinical utility in diagnosing congenital disorders of glycosylation.

References

• European Journal of Human Genetics • 2023 • Compound heterozygous variants in MAN2B2 identified in a Chinese child with congenital disorders of glycosylation PMID:35637269
• Molecular Genetics & Genomic Medicine • 2024 • Congenital disorders of glycosylation with multiorgan disruption and immune dysregulation caused by compound heterozygous variants in MAN2B2 PMID:38622837

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