Similarity of Phenotype in Three Male Patients With the c.320A>G Variant in ALG13: Possible Genotype–Phenotype Correlation

TL;DR

Three males with the same ALG13 gene variant show similar symptoms, suggesting a link between this specific genetic change and a shared condition.

Contribution

Identifies a possible genotype–phenotype correlation for the c.320A>G variant in ALG13 in males.

Findings

Three males with the c.320A>G variant in ALG13 share a consistent phenotype including infantile spasms and drug-resistant epilepsy.

The observed phenotype is not commonly seen in males with other ALG13 pathogenic variants.

The findings suggest a specific genotype–phenotype correlation for the c.320A>G variant in ALG13.

Abstract

Congenital disorders of glycosylation (CDG) are a group of neurometabolic diseases that result from genetic defects in the glycosylation of proteins and/or lipids. Multiple pathogenic genes contribute to the varying reported phenotypes of individuals with CDG‐1 syndromes, most of which are inherited as autosomal recessive traits, although X‐linked inheritance has also been reported. Pathogenic variants in the asparagine‐linked glycosylation 13 homolog (ALG13) gene have been implicated in the aetiology of developmental and epileptic encephalopathy (DEE) 36 (OMIM:*300776, DEE36). The NM_001099922.3:c.320A>G; p.(Asn107Ser) variant is the most frequently described pathogenic variant in ALG13, with 59 females and 2 males with this variant reported to date.

We report on a male with a de novo, hemizygous variant in ALG13: c.320A>G; p.(Asn107Ser), whose phenotype resembles that of two previously reported males with the same variant.

All three males have a de novo mutation, infantile spasms, DEE, drug‐resistant epilepsy, intellectual disability, dysmorphic findings, recurrent infections, skeletal anomalies, brain abnormalities and a movement disorder: a phenotype not consistently reported in males with other pathogenic variants in ALG13.

The similarity of phenotype in the three males with the c.320A>G variant in ALG13, suggests a possible genotype–phenotype correlation.

We report on a male with a de novo, hemizygous variant in ALG13: c.320A>G; p.(Asn107Ser), whose phenotype resembles that of two previously reported males with the same variant. All have a de novo mutation, infantile spasms, developmental and epileptic encephalopathy, drug‐resistant epilepsy, intellectual disability, dysmorphic findings, recurrent infections, skeletal anomalies, brain abnormalities and a movement disorder: a phenotype not consistently reported in males with other pathogenic variants in ALG13.

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