Clinical findings in a carrier of a new mutation in the choroideremia gene

CHM gene molecular analysis and X‐chromosome inactivation pattern determination in two families with choroideremia

“…Although typically only males are affected by the disease, several cases of manifesting choroideremia females have been reported [Shapira and Sitney, 1943;Fraser and Friedmann, 1968;K€ arn€ a, 1986;Majid et al, 1998;Endo et al, 2000;Renner et al, 2006]. The most reasonable explanation for the occurrence of choroideremia manifesting heterozygous females is an unfavorable or skewed X-lyonization mechanism inactivating preferentially the X chromosome carrying the normal CHM allele with the mutant allele expressing in the majority of retinal cells [Jay, 1985;Cheung et al, 2004;Potter et al, 2004]. In this study we performed molecular investigation of the CHM gene in two Mexican families with the disease and analyzed the pattern of X-chromosome inactivation in a number of heterozygous female carriers, including one manifesting female.…”

“…Heterozygous females have no or milder symptoms associated with funduscopically evident patchy areas of chorioretinal degeneration [K€ arn€ a, 1986;Heckenlively and Bird, 1988;Flannery et al, 1990;Rudolph et al, 2003], presumably related to the pattern of X-chromosome inactivation [Flannery et al, 1990;MacDonald et al, 1997]. However, exceptional carrier females fully affected by choroideremia have been also described [Shapira and Sitney, 1943;Fraser and Friedmann, 1968;K€ arn€ a, 1986;Majid et al, 1998;Endo et al, 2000;Renner et al, 2006], these cases apparently arising due to non-random or skewed X-chromosome lyonization preferentially inactivating the chromosome carrying the normal allele [Jay, 1985;Potter et al, 2004].…”

Clinical Characteristics and Current Therapies for Inherited Retinal Degenerations

“…Female carriers are usually asymptomatic, but retinal exams may show a characteristic fundus appearance with irregular pigmentation on the fundus. Despite these widespread changes in the fundus, ERG is normal in female carriers ("dirty fundus, normal function"), although some cases of retinal degeneration have been reported (Potter et al 2004). Night blindness occurring in early childhood is usually the first symptom of the disease.…”

A novel mutation (967−970+2)delAAAGGT in the choroideremia gene found in a Japanese family and related clinical findings

“…[23][24][25][26] Some carriers show very severe cases; for example, one female carrier, age 52, with visual acuity of hand movement and manifesting choroideremia with distinct chorioretinal atrophy has been reported. 25 Another female carrier displayed highly abnormal RPE without the atrophy typical of choroideremia but with severe loss of visual acuity.…”

“…25 Another female carrier displayed highly abnormal RPE without the atrophy typical of choroideremia but with severe loss of visual acuity. 26 These phenotype variations occur because one X chromo- showed fi ne peppery RPE mottling in the mid-periphery. Optic disc, retinal vessels, and macula were normal in both eyes (1992, carrier, age 28).…”