Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026827 (hypotonia)
 5,860 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We describe two unreported types of congenital disorders of glycosylation (CDG) which are caused by mutations in different isoforms of the catalytic subunit of the oligosaccharyltransferase (OST). Each isoform is encoded by a different gene (STT3A or STT3B), resides in a different OST complex and has distinct donor and acceptor substrate specificities with partially overlapping functions in N-glycosylation. The two cases from unrelated consanguineous families both show neurologic abnormalities, hypotonia, intellectual disability, failure to thrive and feeding problems. A homozygous mutation (c.1877T > C) in STT3A causes a p.Val626Ala change and a homozygous intronic mutation (c.1539 + 20G > T) in STT3B causes the other disorder. Both mutations impair glycosylation of a GFP biomarker and are rescued with the corresponding cDNA. Glycosylation of STT3A- and STT3B-specific acceptors is decreased in fibroblasts carrying the corresponding mutated gene and expression of the STT3A (p.Val626Ala) allele in STT3A-deficient HeLa cells does not rescue glycosylation. No additional cases were found in our collection or in reviewing various databases. The STT3A mutation significantly impairs glycosylation of the biomarker transferrin, but the STT3B mutation only slightly affects its glycosylation. Additional cases of STT3B-CDG may be missed by transferrin analysis and will require exome or genome sequencing.
...
PMID:Mutations in STT3A and STT3B cause two congenital disorders of glycosylation. 2384 55

Congenital glycosylation disorders (CDG) are a group of rare hereditary metabolic diseases that result from abnormal protein and lipid glycosylation. Virtually all organ systems can be affected, and neurological involvement is particularly severe and disabling. More than 100 CDG types have been reported to date and those numbers are rapidly increasing. Each type is very rare, and the clinical characteristics of each subtype are difficult to determine. There are large numbers of biochemically unresolved cases defined as CDGIx. In this report, we present a 5-year-old boy who had dysmorphic features, hypotonia, developmental and mental delay, epileptic spasms, recurrent apnea and respiratory failure that led to the diagnosis of an unreported mutation of a rare form of CDG-Ix. This mutation in the STT3B gene affects the catalytic subunit of the oligosaccharyltransferase and the recipient substrate properties, which in part have the same functions in N-glycosylation. A novel homozygous mutation in the STT3B presence of c.38C > G that encodes p.S13W (p.Ser13Trp) was detected with next generation sequencing. The CDG clinical spectrum can be unusual, ranging from dysfunction of certain organs to severe multiple system disorders. Respiratory failure has rarely been reported in these cases. Increased types and numbers of patients constitute symptom variety. The identification of new genes and genotype-phenotype relationships may expand the family of CDG.
 ...
PMID:Novel mutation and severe respiratory failure in congenital disorders of glycosylation Type Ix. 3225 75