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Severe Ciliopathy-Like Phenotype in an Infant With a Novel MPDU1 Missense Variant
Sihem Darouich1,2, Houda Bellamine3, Ichrak Khamassi1,4
1Université de Tunis El Manar, Faculté de Médecine de Tunis, Tunis, Tunisie.
Insights
Congenital disorders of glycosylation (CDG) can cause ciliopathy-like symptoms. A novel MPDU1 gene variant was identified in an infant with severe developmental issues, suggesting CDG in ciliopathy diagnoses.
Area of Science:
- Genetics
- Molecular Biology
- Developmental Biology
Background:
- Congenital disorders of glycosylation (CDG) are linked to ciliary dysfunction.
- Altered glycosylation of ciliary glycoproteins is a known mechanism for CDG-related ciliopathies.
Purpose of the Study:
- To report a novel MPDU1 gene variant associated with a severe ciliopathy-like phenotype.
- To highlight the importance of considering CDG in the differential diagnosis of infantile ciliopathy.
Main Methods:
- Case report of a female infant with a severe ciliopathy-like phenotype.
- Genetic analysis to identify a novel homozygous missense variant in the MPDU1 gene (NM_004870.4:c.503G>A/p.Gly168Glu).
- In-silico analysis and co-segregation studies to confirm the variant's pathogenicity.
Main Results:
- A novel homozygous missense variant (p.Gly168Glu) in the MPDU1 gene was identified.
- The infant presented with a severe ciliopathy-like phenotype including growth restriction, facial dysmorphism, ichthyosis, hepatomegaly with duct plate malformation, renal cysts, cerebral dilatation, and pontocerebellar hypoplasia.
- The identified MPDU1 variant co-segregated with the observed phenotype.
Conclusions:
- The novel MPDU1 missense variant is implicated in a severe infantile ciliopathy-like disorder.
- Congenital disorders of glycosylation (CDG) should be considered in the diagnostic workup of infants presenting with ciliopathy-like conditions.
- This finding expands the genotypic and phenotypic spectrum of CDG and ciliopathies.
Abstract:
Congenital disorders of glycosylation (CDG) are associated with ciliary dysfunction due to altered glycosylation of ciliary glycoproteins. We describe a severe ciliopathy-like phenotype in a female infant associated with a novel homozygous missense variant NM_004870.4(MPDU1):c.503G>A/p.Gly168Glu. Our findings, based on the co-segregation of the variant with the phenotype and in-silico analysis, implicate this MPDU1 missense variant in this disorder. Matched phenotype includes symmetric growth restriction, facial dysmorphism, ichthyosis, hepatomegaly with severe duct plate malformation, renal cortical tubular and glomerular cysts, moderate cerebral tetraventricular dilatation, and severe pontocerebellar hypoplasia. According to this observation, CDG should be included in the workup of infantile ciliopathy-like disorder.
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