ALG3-CDG: lethal phenotype and novel variants in Chinese siblings

Area of Science:

• Genetics
• Biochemistry
• Developmental Biology

Background:

• Congenital disorders of glycosylation (CDG) are a group of rare genetic diseases affecting protein and lipid modification.
• ALG3-CDG is a specific type of CDG, impacting the N-glycosylation pathway.
• These disorders often manifest with multisystemic involvement, particularly affecting the central nervous system.

Purpose of the Study:

• To report a novel genetic cause of severe ALG3-CDG.
• To describe the clinical phenotype and genetic findings in two affected siblings.

Main Methods:

• Whole-exome sequencing was performed to identify the genetic variants.
• Segregation analysis was conducted to confirm inheritance patterns.

Main Results:

• Two siblings exhibited a severe phenotype consistent with ALG3-CDG, including intrauterine death.
• Novel compound heterozygous variants in the ALG3 gene were identified: c.512G>T (p.Arg171Leu) from the mother and c.511C>T (p.Arg171Trp) from the father.

Conclusions:

• This study identifies new pathogenic variants in ALG3, expanding the mutational spectrum of ALG3-CDG.
• The findings underscore the critical role of ALG3 in human development and the severe consequences of its deficiency.