Clinical and molecular spectrum of congenital disorders of glycosylation in 80 Egyptian patients.

Bi-allelic (94%) or X-linked (6%) variants in 29 glycosylation genes, mainly SRD5A3, PMM2 and ALG1

This Egyptian series includes 80 patients from 57 families with molecular findings consistent with a congenital disorder of glycosylation (CDG), with consanguinity in 90% of families. The most frequent features were global developmental delay (98%), dysmorphic facies (86%), hypotonia (85%), movement disorders (48%) and seizures (42%), with frequent structural brain anomalies (thin corpus callosum, cortical and cerebellar atrophy, white matter abnormalities, cerebellar vermis hypoplasia). Bi-allelic variants were found in 94% of patients and X-linked variants in 6%; 53 variants in 29 genes were identified, 38 (72%) of them novel, most frequently in SRD5A3 (16%), PMM2 (11%), ALG1 (10%), NGLY1 (7.5%), MGAT2 (6%) and ALG11 (5%). Two siblings homozygous for a CAMLG missense variant, previously described in a single case, support its role in a new CDG type; a case of UGGT1-CDG is also described and ALG10 is proposed as a candidate gene.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

The gene distribution, led by SRD5A3 rather than PMM2, is a reminder that relative CDG frequencies depend on the population and consanguinity rate. The second familial case of CAMLG helps consolidate this gene, but ALG10 remains a proposal to be confirmed by further families and functional data. The 38 novel variants enrich exome/genome interpretation references for a population under-represented in databases.

Analysis by Dr Thibaut Benquey