A nonsense mutation in PDE6H causes autosomal-recessive incomplete achromatopsia.
Am J Hum Genet
; 91(3): 527-32, 2012 Sep 07.
Article
in En
| MEDLINE
| ID: mdl-22901948
ABSTRACT
Achromatopsia (ACHM) is an autosomal-recessive retinal dystrophy characterized by color blindness, photophobia, nystagmus, and severely reduced visual acuity. Its prevalence has been estimated to about 1 in 30,000 individuals. Four genes, GNAT2, PDE6C, CNGA3, and CNGB3, have been implicated in ACHM, and all encode functional components of the phototransduction cascade in cone photoreceptors. Applying a functional-candidate-gene approach that focused on screening additional genes involved in this process in a cohort of 611 index cases with ACHM or other cone photoreceptor disorders, we detected a homozygous single base change (c.35C>G) resulting in a nonsense mutation (p.Ser12(∗)) in PDE6H, encoding the inhibitory γ subunit of the cone photoreceptor cyclic guanosine monophosphate phosphodiesterase. The c.35C>G mutation was present in three individuals from two independent families with a clinical diagnosis of incomplete ACHM and preserved short-wavelength-sensitive cone function. Moreover, we show through immunohistochemical colocalization studies in mouse retina that Pde6h is evenly present in all retinal cone photoreceptors, a fact that had been under debate in the past. These findings add PDE6H to the set of genes involved in autosomal-recessive cone disorders and demonstrate the importance of the inhibitory γ subunit in cone phototransduction.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Color Vision Defects
/
3',5'-Cyclic-GMP Phosphodiesterases
/
Codon, Nonsense
Type of study:
Etiology_studies
/
Risk_factors_studies
Limits:
Adult
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
Am J Hum Genet
Year:
2012
Document type:
Article
Affiliation country:
Germany