期刊
AMERICAN JOURNAL OF HUMAN GENETICS
卷 91, 期 3, 页码 527-532出版社
CELL PRESS
DOI: 10.1016/j.ajhg.2012.07.006
关键词
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资金
- Deutsche Forschungsgemeinschaft [KFO134-Ko2176/1-2, KFO134-Ru571/5-2]
- Bundesministerium fur Bildung und Forschung [HOPE: 01GM0850, 01GM1108A]
- Foundation Fighting Blindness, USA [BR-GE-0510-0489-RAD, C-GE-0811-0545-RAD01]
- Netherlands Organization for Health Research and Development (ZonMW) [40-00812-98-09047]
- Research Foundation Flanders (FWO) [FWO11/KAN/013-31524611]
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 gamma 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 gamma subunit in cone phototransduction.
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