Malformations of cortical development

Gene: COL3A1

Green List (high evidence)

The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.

Created: 26 Sep 2024, 3:46 p.m. | Last Modified: 26 Sep 2024, 3:46 p.m.

Panel Version: 6.3

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Green List (high evidence)

Comment on list classification: Promoting this gene to amber, with a recommendation for green rating following GMS review.

Created: 25 May 2024, 9:16 p.m. | Last Modified: 25 May 2024, 9:16 p.m.

Panel Version: 5.5

Associated with Polymicrogyria with or without vascular-type EDS in OMIM (OMIM:618343) with a autosomal recessive mode of inheritance.

Several cases reported:

PMID: 19455184 Plancke et al 2009 - report an 11 year old female with consangiuneous parents, who had vascular EDS. The phenotype also included diffuse cortical dysplasia. A homozygous nucleotide duplication (c.479dupT) in COL3A1 resulting in a premature termination codon (p.Lys161GlnfsX45) was identified. Both parents were heterozygous for this variant.

PMID: 25205403 Jørgensen et al 2015 - report 2 siblings who are compound heterozygous for COL3A1 sequence variants. One sibling died suddenly due to extensive aortic dissection at age 15. The younger sibling was cerebral cortical dysplasia with thickened frontoparietal cortices bilaterally, small gyri and findings consistent with pachy micropolygyria

PMID:28742248 - Horn et al 2017 identified biallelic COL3A1 variants in two unrelated families. A 3-year-old female with developmental delay was compound het for a nonsense variant c.1282C>T, p.(Arg428*) and a frameshift variant c.2057delC, p.(Pro686Leufs*105). The patient phenotype at birth was bilateral clubfoot, joint laxity, and dysmorphic facial features an at age 2 years cerebral MRI showed a profound cerebral abnormalities including bilateral frontoparietal polymicrogyria of the cobblestone variant. In the second family (born of unrelated parents from Chechnya and Ingushetia), the two affected siblings were homozygous for the missense variant c.145C<G, p.(Pro49Ala) of COL3A1 and showed cobblestone-like cortical malformation, cerebellar cysts, and white matter abnormalities, developmental delay, and seizures.

PMID: 28258187 - Vandervore et al 2017 - exome analysis of a family with unrelated parents from the same mountain village in Chechnya, consisting of two affected and two non-affected siblings identified a novel homozygous variant c.145C>G (p.Pro49Ala) in exon 2 of COL3A1 in the affected siblings. Both patients had cobblestone-like malformation of the cortex and the white matter was severely abnormal.

Created: 25 Mar 2024, 8:41 p.m. | Last Modified: 25 May 2024, 9:15 p.m.

Panel Version: 5.4

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Polymicrogyria with or without vascular-type EDS, OMIM:618343; polymicrogyria with or without vascular-type Ehlers-Danlos syndrome, MONDO:0032688

Publications

• 19455184
• 25205403
• 28742248
• 28258187