The CHM gene at Xq21.2 codes for the 653 amino acid Rab proteins geranylgeranyltransferase component A 1. There are two known isoforms and one forms the substrate-binding subunit of the Rab geranylgeranyltransferase (GGTase) trimer complex.
Dysfunctional mutations cause choroideremia (OMIM:303100), an X-linked recessive disease characterized by a slowly progressive degeneration of the choroid, photoreceptors, and retinal pigment epithelium. Presentation is typically with night blindness in teenage males followed by loss of peripheral vision and complete blindness by middle age. Carrier females are generally asymptomatic but fundoscopic examination may show patchy areas of chorioretinal atrophy. The standard of care in males seems increasingly likely to include gene therapy with nonmutated CHM in an AAV vector (AAV.REP1) by subfoveal injection as in 2016 it was reported that preserved if not improved visual function at 3.5 year follow up had occurred.
- ↑ Sanchez-Alcudia R, Garcia-Hoyos M, Lopez-Martinez MA, Sanchez-Bolivar N, Zurita O, Gimenez A, Villaverde C, Rodrigues-Jacy da Silva L, Corton M, Perez-Carro R, Torriano S, Kalatzis V, Rivolta C, Avila-Fernandez A, Lorda I, Trujillo-Tiebas MJ, Garcia-Sandoval B, Lopez-Molina MI, Blanco-Kelly F, Riveiro-Alvarez R, Ayuso C. A Comprehensive Analysis of Choroideremia: From Genetic Characterization to Clinical Practice. PloS one. 2016; 11(4):e0151943.(Epub) (Link to article – subscription may be required.)
- ↑ Edwards TL, Jolly JK, Groppe M, Barnard AR, Cottriall CL, Tolmachova T, Black GC, Webster AR, Lotery AJ, Holder GE, Xue K, Downes SM, Simunovic MP, Seabra MC, MacLaren RE. Visual Acuity after Retinal Gene Therapy for Choroideremia. The New England journal of medicine. 2016 Apr 27.(Epub ahead of print) (Link to article – subscription may be required.)