How to cite this article: Perez-Cano HJ, Garnica-hayashi RE, Zenteno JC. 2009. CHM gene molecular analysis and X-chromosome inactivation pattern determination in two families with choroideremia. Am J Med Genet Part A 149A:2134–2140.
CHM gene molecular analysis and X-chromosome inactivation pattern determination in two families with choroideremia†
Version of Record online: 16 SEP 2009
Copyright © 2009 Wiley-Liss, Inc.
American Journal of Medical Genetics Part A
Volume 149A, Issue 10, pages 2134–2140, October 2009
How to Cite
Perez-Cano, H. J., Garnica-hayashi, R. E. and Zenteno, J. C. (2009), CHM gene molecular analysis and X-chromosome inactivation pattern determination in two families with choroideremia. Am. J. Med. Genet., 149A: 2134–2140. doi: 10.1002/ajmg.a.32727
- Issue online: 24 SEP 2009
- Version of Record online: 16 SEP 2009
- Manuscript Accepted: 17 DEC 2008
- Manuscript Received: 1 APR 2008
- retinal dystrophy;
- female carrier
Choroideremia is an X-linked recessive retinal dystrophy characterized by progressive loss of the photoreceptor, the retinal pigment epithelium, and the choriocapillaris layers which ultimately can result in blindness by the fifth decade of life. The disease is caused by mutations in the gene CHM, which encodes a protein involved in the regulation of intracellular vesicular traffic. Typically, hemizygous males are affected by the disease and female carriers are asymptomatic with only a diffuse mottled pattern of hyperpigmentation on funduscopy. Uncommon instances of fully affected females have been described previously and these cases are proposed to arise from an skewed Lyonization mechanism preferentially inactivating the X chromosome carrying the normal CHM allele. In this work, the clinical and molecular features of two Mexican families with choroideremia are described. A novel and a previously described CHM mutation were identified. X-chromosome inactivation assays were performed in a total of 12 heterozygous carriers from the two families. In an affected female from family A, a random X-inactivation pattern was demonstrated; on the other hand, in a female carrier from family B displaying a conspicuous pattern of pigment epithelium mottling at the peripheral retina, a skewed X-inactivation pattern was found. However, the X-chromosome preferentially inactivated in this female was the one carrying the mutated allele. Our results add to the genotypic spectrum in choroideremia and does not support a correlation between X-inactivation status and abnormal retinal phenotype in heterozygous female carriers from these two families. © 2009 Wiley-Liss, Inc.