Alternative titles; symbols
HGNC Approved Gene Symbol: PDE6H
Cytogenetic location: 12p12.3 Genomic coordinates (GRCh38): 12:14,973,042-14,981,865 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 12p12.3 | Achromatopsia 6 | 610024 | Autosomal dominant; Autosomal recessive | 3 |
| Retinal cone dystrophy 3 | 610024 | Autosomal dominant; Autosomal recessive | 3 |
Shimizu-Matsumoto et al. (1996) reported the isolation of a cDNA, which they designated PDE6H, from a human retinal library. The sequence predicted an 83-amino acid protein with near identity to the bovine blue cone cGMP phosphodiesterase gamma subunit (Hamilton and Hurley, 1990). Northern blot analysis confirmed retinal expression, and in situ hybridization showed specificity of the mRNA to the cones.
By double immunofluorescence labeling of mouse retina, Kohl et al. (2012) demonstrated that Pde6h is exclusively located in cone photoreceptors and is present in all 3 cone types (L, M, and S).
By fluorescence in situ hybridization, Shimizu-Matsumoto et al. (1996) mapped the PDE6H gene to chromosome 12p13.
Retinal Cone Dystrophy 3A
In 2 sibs with a distinctive form of cone dystrophy (RCD3A; 610024) characterized by decreased central vision, atrophic macular lesions, night blindness, and supernormal and delayed rod responses on scotopic electroretinogram testing, Piri et al. (2005) identified a heterozygous G-to-C substitution in the 5-prime untranslated region of the PDE6H gene (601190.0001).
Achromatopsia 6
In a Dutch man and 2 Belgian sibs with incomplete achromatopsia (ACHM6; see 610024), Kohl et al. (2012) identified homozygosity for a nonsense mutation in the PDE6H gene (S12X; 601190.0002). The authors estimated that mutations in PDE6H account for only about 0.3% of all autosomal recessive cases of ACHM.
In 2 sibs with retinal cone dystrophy-3 (610024), Piri et al. (2005) identified heterozygosity for a G-to-C transversion in the 5-prime UTR (29 nucleotides upstream of the translation start codon) of the PDE6H gene. Although the mutation was not found in 95 normal individuals tested, it was found in the patient's unaffected father. The patient's mother and unaffected sibs were not available for study. Piri et al. (2005) speculated that the affected sibs may be compound heterozygotes, with another mutation in the PDE6H gene or in a different gene, or that genetic factors present only in the father may mitigate the phenotypic expression of the disease.
In a Dutch man and a Belgian brother and sister with incomplete achromatopsia (ACHM6; see 610024), Kohl et al. (2012) identified homozygosity for a 35C-G transversion in exon 2 of the PDE6H gene, resulting in a ser12-to-ter (S12X) substitution predicted to result in a truncated protein of only 11 amino acids. The Belgian parents were heterozygous for the mutation, which was not found in any database query. Kohl et al. (2012) noted that the protein would likely represent a functional null allele, as it would lack all conserved domains relevant for transducin binding and inhibition of the catalytic activity of PDE; however, it was predicted to undergo nonsense-mediated decay. Haplotype analysis identified a common 301-kb haplotype flanked by rs111596034 (D12S2210) and rs2430621, suggesting that the S12X mutation resulted from a common ancestral mutational event in the 2 families.
Hamilton, S. E., Hurley, J. B. A phosphodiesterase inhibitor specific to a subset of bovine retinal cones. J. Biol. Chem. 265: 11259-11264, 1990. [PubMed: 2162841]
Kohl, S., Coppieters, F., Meire, F., Schaich, S., Roosing, S., Brennenstuhl, C., Bolz, S., van Genderen, M. M., Riemslag, F. C. C., the European Retinal Disease Consortium, Lukowski, R., den Hollander, A. I., Cremers, F. P. M., De Baere, E., Hoyng, C. B., Wissinger, B. A nonsense mutation in PDE6H causes autosomal-recessive incomplete achromatopsia. Am. J. Hum. Genet. 91: 527-532, 2012. [PubMed: 22901948] [Full Text: https://doi.org/10.1016/j.ajhg.2012.07.006]
Piri, N., Gao, Y. Q., Danciger, M., Mendoza, E., Fishman, G. A., Farber, D. B. A substitution of G to C in the cone cGMP-phosphodiesterase gamma subunit gene found in a distinctive form of cone dystrophy. Ophthalmology 112: 159-166, 2005. [PubMed: 15629837] [Full Text: https://doi.org/10.1016/j.ophtha.2004.07.011]
Shimizu-Matsumoto, A., Itoh, K., Inazawa, J., Nishida, K., Matsumoto, Y., Kinoshita, S., Matsubara, K., Okubo, K. Isolation and chromosomal localization of the human cone cGMP phosphodiesterase gamma cDNA (PDE6H). Genomics 32: 121-124, 1996. [PubMed: 8786098] [Full Text: https://doi.org/10.1006/geno.1996.0085]