Structural eye disease

Gene: HNRNPC

I don't know

Comment on list classification: There are only two unrelated patients reported with monoallelic HNRNPC variants and bilateral colobomatous microphthalmia. They were both identified with the same missense variant, the only functional evidence available for this variant is from in silico structural modelling. Hence, this gene can only be rated amber with the current evidence.

Created: 15 Aug 2025, 3:05 p.m. | Last Modified: 15 Aug 2025, 3:06 p.m.

Panel Version: 4.20

PMID:37541189 (2023) reported a cohort of 13 individuals with heterozygous germline variants in HNRNPC gene, including a recurrent de novo in-frame deletion in five individuals (c.850_876del/ p.(Arg284_Asp292del) for HNRNPC-iso1 and c.889_915del/ p.(Arg297_Asp305del) for HNRNPC-iso2). They all presented with a neurodevelopmental disorder characterised by global developmental delay, intellectual disability, behavioural abnormalities, and subtle facial dysmorphic features in most individuals. The only patient with the p.(Arg99Gln) missense variant had bilateral colobomatous microphthalmia and bilateral cochlear malformations.

PMID:40004505 (2025) reported the identification of the same missense variant (p.(Arg99Gln)) in a patient showing a unique clinical presentation characterised by DD/ID, distinctive facial features, cochlear aplasia, and bilateral colobomatous microphthalmia. The clinical phenotype of this individual fit that of the previously described individual with the same variant from PMID:37541189, and only partially overlaps with the clinical spectrum of the disease. There is some functional evidence available for this variant from in silico structural modelling.

This gene has already been associated with relevant phenotypes in OMIM (MIM #620688), but not yet in Gene2Phenotype.
Sources: Literature

Created: 15 Aug 2025, 3:02 p.m. | Last Modified: 15 Aug 2025, 3:38 p.m.

Panel Version: 4.20

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Intellectual developmental disorder, autosomal dominant 74, OMIM:620688; microphthalmia, isolated, with coloboma, MONDO:0000170

Publications

• 37541189
• 40004505