Congenital Disorders of Glycosylation
Gene: SEC23A
SEC23A is an essential component of coat protein complex II (COPII)-coated vesicles that transport secretory proteins from the endoplasmic reticulum (ER) to the Golgi complex.
One family has been reported (PMID:16980979) with a homozygous missense variant and craniolenticulosutural dysplasia (CLSD), with some functional studies supporting pathogenicity.
The same authors later reported another individual with similar phenotype with a paternally inherited heterozygous missense variant, this variant has 91 hets in gnomAD and the father was unaffected (PMID: 21039434). They suggest digenic inheritance but found no other variants in 3 candidate genes.
Zebrafish models lend some support to the gene-disease association (PMID:16980979, 16980978).
This is the only reference to CDG I can find: Two individuals from the same consanguineous family were found to have biallelic variants in SEC23A and MAN1B1 (PMID: 27148587). Patients presented with carbohydrate-deficient transferrin, tall stature, obesity, macrocephaly, and maloccluded teeth (CLSD individuals present with short stature). Parents were healthy carriers for both variants and an unaffected sibling with tall stature carried the heterozygous variant in SEC23A only. The MAN1B1 variant has been previously associated with CDG and short stature. Normal SEC23A levels were identified for all family members. Pro-COL1A1 secretion was increased in patients and siblings. The authors postulate that the SEC23A variants are contributing to the tall stature in the family due to increased pro-COL1A1 secretion, and that this is a digenic disease, but I'm not very convinced.
This gene is not green in any GEL panels. It is on the Invitae CDG panel.
I don't think there is enough evidence for a gene-disease association let alone association with CDG.Created: 22 Jul 2020, 2:23 a.m. | Last Modified: 22 Jul 2020, 2:24 a.m.
Panel Version: 0.96
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Craniolenticulosutural dysplasia (MIM# 607812)
Publications
Variants in this GENE are reported as part of current diagnostic practice
Gene: sec23a has been classified as Red List (Low Evidence).
Phenotypes for gene: SEC23A were changed from to Craniolenticulosutural dysplasia (MIM# 607812)
Publications for gene: SEC23A were set to
Mode of inheritance for gene: SEC23A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Gene: sec23a has been classified as Red List (Low Evidence).
gene: SEC23A was added gene: SEC23A was added to Congenital Disorders of Glycosylation_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services Mode of inheritance for gene: SEC23A was set to Unknown