Structural eye disease

Gene: CAPN15

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

Created: 8 Mar 2022, 10:32 a.m. | Last Modified: 8 Mar 2022, 10:32 a.m.

Panel Version: 1.113

Comment on publications: Mor-Shaked et al. 2021 (PMID:33410501) report a fifth family with 2 sibs who harboured a homozygous 47 base-pair deletion in a minimal intron of CAPN15. Both patients presented with microphthalmia, and one individual also had a right iris coloboma and bilateral optic gliosis

Created: 10 Jun 2021, 2:39 p.m. | Last Modified: 10 Jun 2021, 2:39 p.m.

Panel Version: 1.71

Comment on phenotypes: CAPN15 is now associated with a relevant phenotype in OMIM - 'Oculogastrointestinal neurodevelopmental syndrome', MIM# 619318

Created: 10 Jun 2021, 2:38 p.m. | Last Modified: 10 Jun 2021, 2:38 p.m.

Panel Version: 1.70

Green List (high evidence)

Zha et al. 2020 described 4 families with structural eye anomalies with biallelic variants segregating + animal model. Mor-Shaked et al. 2021 add two siblings with biallelic variant affecting splice donor site and eye abnormalities

Created: 20 Jan 2022, 11:38 a.m. | Last Modified: 20 Jan 2022, 11:38 a.m.

Panel Version: 1.101

Zha et al. 2020 described 4 families with structural eye anomalies with biallelic variants segregating + animal model

Created: 20 Jan 2021, 10:29 a.m. | Last Modified: 20 Jan 2021, 10:29 a.m.

Panel Version: 1.29

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

• 32885237
• 33410501

Green List (high evidence)

Comment on list classification: Promoting gene from red to amber, but with recommendation for green rating following GMS review.

Created: 2 Dec 2020, 4:05 p.m. | Last Modified: 2 Dec 2020, 4:05 p.m.

Panel Version: 1.20

Publication relating to previous conference abstract now available:
PMID: 32885237 - Zha et al 2020 - report 5 individuals with microphthalmia and/or coloboma from 4 independent families who, through WES, were identified as carrying homozygous or compound heterozygous missense variants in CAPN15 that are predicted to be damanging. the variants segregated with the disease in all 4 families, with parents being unaffected heterozygous carriers. Several individuals had additional phenotypes including growth deficits (2 families), developmental delay (2 families) and hearing loss (2 families). Capn15 knockout mice showed similar severe developmental eye defects, including anophthalmia, microphthalmia and cataract, and diminished growth.

Created: 2 Dec 2020, 4:05 p.m. | Last Modified: 2 Dec 2020, 4:15 p.m.

Panel Version: 1.22

Conference talk/abstract from ESHG2020 - C06.4 - Mouse and human studies support a role for CAPN15 variants in cataract and microphthalmia - Zha et al. Describe a Capn15 mouse knockout with cataract and microphthalmia, and three human cases with phenotypes including growth delay (2/3), cataracts (1/3), coloboma (2/3) and microphthalmia (2/3). They were identified with homozygous or compound heterozygous likely pathogenic variants in CAPN15.
No publication relating to this work has been identified in PubMed at this time.
Sources: Literature

Created: 13 Jun 2020, 7:22 a.m. | Last Modified: 13 Jun 2020, 7:23 a.m.

Panel Version: 1.8

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
microphthalmia HP:0000568; coloboma HP:0000589

Publications

• 32885237