Similarity of phenotype in three male patients with the c.320A>G variant in <i>ALG13</i>: possible genotype-phenotype correlation

<p dir="ltr"><b>Background:</b> 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 (<i>ALG13</i>) 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 <i>ALG13</i>, with 59 females and 2 males with this variant reported to date. <p dir="ltr"><b>Methods:</b> We report on a male with a de novo, hemizygous variant in <i>ALG13</i>: c.320A>G; p.(Asn107Ser), whose phenotype resembles that of two previously reported males with the same variant. <p dir="ltr"><b>Results:</b> 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<i> ALG13</i>. <p dir="ltr"><b>Conclusion:</b> The similarity of phenotype in the three males with the c.320A>G variant in<i> ALG13</i>, suggests a possible genotype-phenotype correlation.