Mackenzie's Mission_Reproductive Carrier Screening

Gene: SEC23A

I don't know

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.

In summary, there is only one family reported with convincing evidence for gene-disease association, and we have downgraded this gene on other panels.

Created: 22 Jul 2020, 6:24 a.m. | Last Modified: 22 Jul 2020, 6:24 a.m.

Panel Version: 0.7

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Craniolenticulosutural dysplasia (MIM# 607812)

Publications

• 16980979
• 21039434
• 16980978
• 27148587