Retinal disordersGene: SEMA4A
PMID: 16199541 identified 2 patients with RP and 2 with cone-rod dystrophy who were compound heterozygous for SEMA4A D345H and F350C. 3 other patients with RP had heterozygous R713Q. PMID: 28805479 reported 3 families with retinal degeneration where the unaffected family members were either homozygous or heterozygous for the R713Q variant. The report concluded that the R713Q variant is insufficient to cause AR/AD RP and unlikely to be pathogenic. PMID: 23360997 shows that knockin mouse model with F350C variant is pathogenic and causes retinal degeneration phenotype. Therefore, there are only 2 cases. This gene has been demoted from green to amber based on literature and expert review.
Created: 30 Aug 2019, 2:52 p.m. | Last Modified: 30 Aug 2019, 2:52 p.m.
Panel Version: 1.160
p.Arg713Gln is too common to cause adCORD. The other missense vriants reported in the paper are rare, although the gene has never been convincingly validated - remove?
Created: 30 Aug 2019, 2:12 p.m. | Last Modified: 30 Aug 2019, 2:12 p.m.
Panel Version: 1.159
The variant reported by Abid et al 2006 (PMID 16199541) associated with adRP (R713Q) has subsequently been shown to be a polymorphism with a high allele frequency in ExAC. I am unaware of any additional retinal dystrophy family reported with recessive disease and biallelic variants in this gene. Therefore, we believe there is little evidence for causality.
Created: 23 Jun 2017, 11:59 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
retinitis pigmentosa; cone-rod dystrophy
This gene is on the Manchester Genetic Retinal Degeneration Conditions panel (covers known genes for isolated progessive retinal degeneration, Leber congenital amaurosis, macular dystrophy, achromatopsia, congenital stationary night blindness as well as the two most common causes of syndromic blindess Usher and Bardet-Biedl syndromes and additional syndromes including Joubert, Senior-Loken, and Cohen syndrome.
Created: 2 Jun 2016, 8:05 a.m.
Source Expert Review Amber was added to SEMA4A. Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Source NHS GMS was added to SEMA4A. Rating Changed from Green List (high evidence) to Green List (high evidence)
Phenotypes for gene: SEMA4A were changed from Achromatopsia, Cone, and Cone-rod Dystrophy; Eye Disorders; Cone-rod dystrophy 10, 610283Retinitis pigmentosa 35, 610282; Retinitis Pigmentosa, Recessive; Retinitis pigmentosa to Achromatopsia, Cone, and Cone-rod Dystrophy; Eye Disorders; Cone-rod dystrophy 10, 610283; Retinitis pigmentosa 35, 610282; Retinitis Pigmentosa, Recessive; Retinitis pigmentosa
Publications for gene: SEMA4A were set to
This gene has been classified as Green List (High Evidence).
Model of inheritance for gene SEMA4A was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
SEMA4A was created by ellenmcdonagh
SEMA4A was added to Posterior segment abnormalitiespanel. Sources: Expert Review Green