Retinal disorders

Gene: RDH5

Green List (high evidence)

Comment on mode of inheritance: Recommendation that the mode of inheritance be updated to Biallelic only. Only 2 cases with single heterozygous variants were reported in a single publication from 2012 with no further cases reported since

Created: 15 Oct 2025, 4:15 p.m. | Last Modified: 15 Oct 2025, 4:15 p.m.

Panel Version: 8.55

Comment on phenotypes: OMIM phenotype accessed on 15th October 2025

Created: 15 Oct 2025, 4:13 p.m. | Last Modified: 15 Oct 2025, 4:13 p.m.

Panel Version: 8.54

Reviewing the mode of inheritance in reported cases:

In OMIM the phenotype Fundus albipunctatus, OMIM:136880 is entered with both AD, AR modes of inheritance. However, only variants with autosomal recessive inheritance are listed https://omim.org/entry/601617.

Numerous reports of cases with biallelic or compound heterozygous variants in RDH5 and a Fundus albipunctatus phenotype (see below).
3 patients reported with monoalleic variants but one can be excluded due to lack of information (PMID: 21529959). From this, the number of monoallelic cases does not reach the threshold of 3 unrelated cases. The lack of further reports of monoallelic cases since the single 2012 report (PMID: 22815624 ) indicates the rarity of single heterozygous variants causing the condition, and perhaps that a second variant was present but undetected in the analysis.

PMID: 21529959 Sergouniotis et al 2011 - 9 patients from 8 families with suggestive RDH5 retinopathy had the RDH5 gene sequenced. Either homozygous or compound heterozygous mutations were detected in RDH5 in 8 patients from 7 families. One patient declined to donate blood, but analysis of her mother’s DNA disclosed heterozygosity for a novel mutation. From this it cannot be determined whether the patient had one or two variants in the gene.

PMID: 22815624 Pras et al 2012 - 20 patients with FAP from 14 families of diverse ethnicities mainly of Jewish decent. RDH5 mutations were found in all patients except one. Notably in two patients only a single heterozygous mutation was identified despite analyzing the 5′ untranslated region of the gene. In these cases further family members reported night blindness or were sequenced.


Examples of biallelic cases:

PMID: 10369264 Yamamoto et al. (1999) - report 2 unrelated patients with Fundus albipunctatus and RDH5 variants. 1 had a homozygous missense change (Gly238Trp), the other was compound heterozygous for 2 missense changes (Gly238Trp, Ser73Phe).

PMID: 10617778 Gonzalez-Fernandez et al. (1999) - report 2 unrelated patients with Fundus albipunctatus - 1 had a homozygous missense change (Gly238Trp), the other was compound heterozygous for 2 missense changes (Arg280His and Ala294Pro). Heterozygous carriers showed no phenotype.

PMID: 25820994 Skorczyk-Werner et al 2015 - literature review and report of one new case where RDH5 was sequenced in a patient with Fundus albipuncatus and a biallelic missense variant was found Tyr175Phe.

PMID: 32232344 Katagiri et al 2020 - Twenty-five patients from 22 Japanese pedigrees with RDH5-related FAP were studied. All had homozygous or compound heterozygous variants in RDH5.

Created: 15 Oct 2025, 4:11 p.m. | Last Modified: 15 Oct 2025, 4:11 p.m.

Panel Version: 8.52

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Fundus albipunctatus, OMIM:136880; fundus albipunctatus, MONDO:0007639

Publications

• 21529959,
• 22815624
• 10369264
• 25820994
• 32232344

Green List (high evidence)

Query the current both MOI?

Created: 2 May 2025, 8 p.m. | Last Modified: 2 May 2025, 8 p.m.

Panel Version: 8.1

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Comment on publications: A domestic cat model with a loss-of-function missense mutation in RDH5 (c.542G > T; p.Gly181Val) has been described in PMID:34726233 and the affected cats have a marked delay in recovery of dark adaptation and develop a degeneration of the area centralis (human equivalent is macula).

In addition, a review of the database of patients with inherited retinal disease at Moorfields Eye Hospital London and The Hospital for Sick Children Toronto identified 17 patients with confirmed biallelic mutations in RDH5. Of these, seven patients (from six families) had macular atrophy evident on SD-OCT and/or fundus autofluorescence imaging.

Created: 10 Feb 2023, 10:11 a.m. | Last Modified: 10 Feb 2023, 10:14 a.m.

Panel Version: 3.31

Green List (high evidence)

Comment on publications: Added publications suggested from external expert review

Created: 13 Jul 2018, 4:03 p.m.

Comment on mode of inheritance: updated MOI from external expert review and OMIM

Created: 13 Jul 2018, 4:02 p.m.

Green List (high evidence)

https://www.omim.org/entry/601617

Created: 1 Jun 2018, 6:05 p.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Publications

• PMID: 21529959

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.