Clinical and genetic features of choroideremia

Background: Choroideremia is an X-linked hereditary eye disease that causes progressive degeneration of the choroid and retina and frequently leads to legal blindness in later life. Recent molecular genetic studies have revealed mutations involving the Rab escort protein (REP-1) gene localized at Xq 21.Clinical Features: The clinical picture and rate of progression may vary among affected individuals in different families and within the same family. Usually, hemizygous males develop night blindness in their teenage years, followed by progressive peripheral visual field constriction and visual disability in late age. Heterozygous female carriers are mostly asymptomatic, but their fundi show characteristic pigment changes in the midperiphery closely resembling the fine mottling observed in the initial stage of the disease in males.Molecular Genetics: Assessment of the REP-1 gene in European and Japanese choroideremia patients has revealed a wide variety of mutations, including gross deletions and point mutations such as nonsense, frameshift, and splice-site mutations. All these mutations are thought to fail in intact REP-1 protein synthesis.Conclusions: The recent molecular studies may open a new chapter in the research on choroideremia as well as diagnosis and genetic counseling.