MAN1B-CDG: Novel variants with a distinct phenotype and review of literature.
Balasubramanian M. and al. Eur J Med Genet. 2018 Jun 14.
Congenital disorders of glycosylation (CDG) are a group of rare metabolic diseases due to impaired lipid and protein glycosylation. It comprises a characteristic high frequency of intellectual disability (ID) and a wide range of clinical phenotypes.
To identify the underlying diagnosis in two families each with two siblings with variable level of ID through trio whole exome sequencing.
Both the families were recruited to the Deciphering Developmental Disorders (DDD) study to identify the aetiology for their ID. Further work-up included isoelectric focusing (IEF) of serum transferrin done to add evidence to the molecular diagnosis.
These patients were found to have three novel variants in MAN1B1 inherited from their healthy parents. Serum transferrin IEF showed a type 2 pattern.
MAN1B1 variants were initially described in association with non-syndromic ID; subsequent literature suggested that variants in MAN1B1 resulted in a CDG-type II syndrome. However, there remains a paucity of literature on detailed clinical phenotyping and it still remains a rare form of CDG. The present patients showed the phenotype previously reported in MAN1B1-CDG: a characteristic facial dysmorphism, hypotonia, truncal obesity and in some, behavioural problems.
In unexplained ID, serum transferrin should be included in the first-line screening. With advances in genomic medicine, it is important to diagnose CDG as this has implications for management and recurrence risk counselling.