Malformations of cortical development

Gene: NFIA

Green List (high evidence)

Comment on list classification: As reviewed by Nour Elkhateeb, there is sufficient evidence available for the promotion of this gene to green rating in the next GMS update.

Created: 19 Jul 2025, 5:54 p.m. | Last Modified: 19 Jul 2025, 5:54 p.m.

Panel Version: 7.6

The ClinGen Brain Malformations expert panel has classified the association of NFIA gene to brain malformations with or without urinary tract defects (MONDO:0100478) as 'Definitive'. More information can be found in https://search.clinicalgenome.org/CCID:005631.

As reviewed in PMID:36553517, there are four unrelated families reported with monoallelic NFIA variants and with cortical malformations.

PMID:27081522 - A de novo truncating variant (p.Pro365Hisfs*32) in the NFIA gene was reported in a five-year-old patient. The CNS malformations reported in the patients include agenesis of corpus callosum, ventricular enlargement, interhemispheric cysts and polymicrogyria in the right frontal lobe.

PMID:28452798 - A proband and her mother were identified with 1.065kb intragenic deletion. The proband had CNS malformations including thin corpus callosum, ventriculomegalyn and frontalcortical malformation with polymicrogyria, while mother had corpus callosum hypoplasia, mild ventriculomegaly and mild frontoparietal atrophy/hypoplasia.

PMID:33973697 - Two unrelated patients were reported with a missense variant in NFIA gene (p.Lys125Glu), of which the 14‐month‐old male patient was reported with corpus callosum hypoplasia, polycerebral gyrus at parasylvius fissures and cortical dysplasia of bilateral cerebral hemisphere.

PMID:36553517 also reported a patient from DECIPHER database with corpus callosum hypoplasia, ventriculomegaly and abnormality of neuronal migration.

This gene has also bee associated with relevant phenotypes in OMIM (MIM #613735) and Gene2Phenotype (with 'strong' rating on the DD panel).

Created: 19 Jul 2025, 5:51 p.m. | Last Modified: 19 Jul 2025, 5:51 p.m.

Panel Version: 7.3

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Brain malformations with or without urinary tract defects, OMIM:613735

Publications

• 27081522
• 28452798
• 33973697
• 36553517

cortical malformations reported in PMID 36553517, and other CNS malformations reported in PMID 36553517 and PMID: 27081522
Sources: Literature

Created: 23 May 2025, 2:44 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Publications

• 36553517,