Retinal disorders

Gene: LAMP2

Green List (high evidence)

The rating of this gene has been updated to Green and the mode of inheritance set to 'X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)' following NHS Genomic Medicine Service approval.

Created: 10 Oct 2023, 10:23 a.m. | Last Modified: 10 Oct 2023, 10:23 a.m.

Panel Version: 4.34

Comment on list classification: As reviewed by Siying Lin (Moorfields Eye Hospital), there is sufficient evidence for this gene to be promoted to GREEN rating at the next GMS update.

Created: 15 May 2023, 6:05 p.m. | Last Modified: 15 May 2023, 6:05 p.m.

Panel Version: 4.8

PMID:16751040 - Four affected females presented with a peripheral pigmentary retinopathy and two affected males presented with a near-complete loss of pigment in the retinal pigment epithelium.

PMID:22290069 - Two siblings with Danon disease and variant in LAMP2 (p.Gly384Arg) had no ocular phenotypes, while a third sibling and a cousin developed cone-rod dystrophy leading to legal blindness.

PMID:26398689 - Four members from a family with Danon disease identified with variant in LAMP2 (c.294G > A) had low electrooculogram voltages, which indicate that the retinal pigment epithelium is unable to maintain its tight junctions.

PMID:32533651 - 10 patients with Danon disease (3 males, 7 females) identified with variant in LAMP2 and manifested with cardiomyopathy had pigmentary retinopathy with altered autofluorescence and diffuse visual field loss.

PMID:32890081 - A 26-year-old woman with Danon disease had outer retinal degeneration, such as thinning of both the photoreceptor and retinal pigment epithelium layers at the fovea.

PMID:36288619 - Three cases from two unrelated families diagnosed with Danon disease and identified with LAMP2 variant were reported with a stereotypical pattern of primary retinal pigment epithelial or parallel retinal pigment epithelial & photoreceptor disease.

This gene has been associated with Danon disease in both OMIM (MIM #300257) and Gene2Phenotype and retinal phenotypes have been documented as part of Danon disease in OMIM.

Created: 15 May 2023, 6:04 p.m. | Last Modified: 15 May 2023, 6:04 p.m.

Panel Version: 4.7

Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

Phenotypes
Danon disease, OMIM:300257

Publications

• 16751040
• 22290069
• 26398689
• 32533651
• 32890081
• 36288619

Green List (high evidence)

Several reports in literature identifying pigmentary retinopathy as part of the phenotypic spectrum in patients with Danon disease (female carriers less severely affected)
Sources: Literature

Created: 8 May 2023, 10:39 p.m.

Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

Phenotypes
Pigmentary retinopathy

Publications

• (PMID: 16751040
• 32533651
• 36288619
• 22290069
• 32890081
• 26398689)

Mode of pathogenicity
Other