Malformations of cortical development

Gene: FIG4

Comment on list classification: Associated with relevant phenotype in OMIM, but not associated with ?Polymicrogyria, bilateral temporooccipital OMIM:612691 in Gen2Phen. A single missense variant has been reported in a large consanguineous Moroccan family, supportive functional studies were also reported (PMID: 24598713).

Created: 13 Aug 2021, 8:37 a.m. | Last Modified: 13 Aug 2021, 8:37 a.m.

Panel Version: 2.49

Comment on phenotypes: FIG4 variants also are associated with Amyotrophic lateral sclerosis 11 OMIM:612577; Charcot-Marie-Tooth disease, type 4J OMIM:611228 and Yunis-Varon syndrome OMIM:216340, but these phenotypes are not appropriate for this panel.

Created: 13 Aug 2021, 8:33 a.m. | Last Modified: 13 Aug 2021, 8:33 a.m.

Panel Version: 2.48

I don't know

One family and a supportive mouse model:

PMID 18758830 – Ben Cheikh et al (2009) studied a large consanguineous Moroccan family in which bilateral occipital polymicrogyria segregated as an autosomal recessive trait, establishing linkage to 6q16-q22 by homozygosity mapping. Three affected individuals had epilepsy and polymicrogyria (other siblings had variable phenotypes).

PMID 24598713 – Baulac et al (2014) analysed the consanguineous Moroccan family and detected a homozygous missense variant in FIG4, which was homozygous in each of the affected siblings with polymicrogyria, heterozygous in one healthy sibling, not present in three healthy siblings, heterozygous in both parents and not tested in a further four siblings. They went on to study transfected fibroblasts from FIG4 deficient mice and examined histologically brains from FIG4-null mice which had findings that included changes “reminiscent of human cortical malformations”.
Sources: Expert list

Created: 27 Aug 2020, 10:45 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Polymicrogyria with epilepsy MIM# 612691

Publications

• 18758830
• 24598713