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Retinitis pigmentosa and common variable immunodeficiency disease: associated or separate?

Retinitis pigmentosa (RP) and common variable immunodeficiency disease (CVID), both debilitating disorders, are genetically and phenotypically heterogenous. (1-3) In this issue of the Southern Medical Journal, Starr and colleagues (4) report their clinical findings of three generations in which both RP and CVID appear to occur together. Retinitis pigmentosa, which can be inherited in an autosomal dominant, autosomal recessive or X-linked manner, is as varied in its phenotypic or clinical presentation as CVID. This clinical and genetic heterogeneity can confound the precise mode of disease transmission, as seen in this family. For instance, the disease in this family could be X-linked recessive or autosomal recessive, where both sexes may be equally affected. In a disease characterized by an X-linked inheritance pattern, males have the disease, whereas females usually carry the disease allele, but do not have the disease. However there are exceptions to this and females can be affected or have a milder form of the disease. Usually when females have some form of disease characterized by an X-linked recessive mode of inheritance, the parents are consanguineous, resulting in an affected daughter being homozygous for the disease allele. However, sometimes it is unknown if the affected individual is from a consanguineous union or even if the parents had the disease, because the phenotype could have been mildly expressed and therefore clinically undetected. Further complicating the situation, severity of disease can differ in family members that have the same genotype, in both types of inheritance patterns, X-linked or autosomal recessive. This is because epidemiologic or other genetic contributions may modify the expression of the disease. There are many examples reported in the literature that demonstrate variable expressivity of a genotype within the same family. This has been observed, for example, in patients with X-linked RP, (5,6) as well as Usher syndrome, an autosomal recessively inherited disease characterized by RP and deafness. (7-9)

In the case presented by Starr et al, in which the sister of the proband in the second generation was diagnosed with CVID, an ophthalmic examination or an electroretinogram (ERG), (which objectively measures the electrical activity of the photoreceptor cells in the retina) might detect a very mild form of RP. If the two diseases are in fact associated or on the same gene that is being transmitted in this family, this would help elucidate the mode of transmission. Sometimes, a characteristic of a severe X-linked disease is the inability to reproduce--possibly evidenced by the diagnosis of the Sertoli-only syndrome in the proband in the case reported here. This previously unreported finding that RP and CVID could occur concomitantly may point to mechanisms that underlie the etiology of either disease. Moreover, it has been hypothesized from a study done in a small group of patients with RP that the elevated amounts of antigens observed in their sera result from the degeneration of the retina and this, in turn, might exacerbate the immune and inflammatory responses observed. (10) Identifying candidate genes and environmental factors that could be used in the development of appropriate targets may be a useful initial step for both preventative and therapeutic interventions in diseases such as retinitis pigmentosa and common variable immunodeficiency disease.


1. Rivolta C, Sharon D, DeAngelis MM, et al. Retinitis pigmentosa and allied diseases: numerous diseases, genes, and inheritance patterns. Hum Mol Genet 2002;11:1219-1227.

2. Weiler CR, Bankers-Fulbright JL. Common variable immunodeficiency: test indications and interpretations. Mayo Clin Proc 2005;80:1187-1200.

3. Rose ME, Lang DM. Evaluating and managing hypogammaglobulinemia. Cleve Clin J Med 2006;73:133-134.

4. Starr JC, Brasher GW, Dominguez J, et al. Retinitis pigmentosa and hypogammaglobulinemia. South Med J 2006;99:989-991.

5. Sharon D, Bruns GA, McGee TL, et al. X-linked retinitis pigmentosa: mutation spectrum of the RPGR and RP2 genes and correlation with visual function. Invest Ophthalmol Vis Sci 2000;41:2712-2721.

6. Sharon D, Sandberg MA, Rabe VW, et al. RP2 and RPGR mutations and clinical correlations in patients with X-linked retinitis pigmentosa. Am J Hum Genet 2003;73:1131-1146.

7. Liu XZ, Hope C, Walsh J, et al. Mutations in the myosin VIIA gene cause a wide phenotypic spectrum, including atypical Usher syndrome. Am J Hum Genet 1998;63:909-912.

8. Zina ZB, Masmoudi S, Ayadi H, et al. From DFNB2 to Usher syndrome: variable expressivity of the same disease. Am J Med Genet 2001;101:181-183.

9. Aller E, Jaijo T, Oltra S, et al. Mutation screening of USH3 gene (clarin-1) in Spanish patients with Usher syndrome: low prevalence and phenotypic variability. Clin Genet 2004;66:525-529.

10. Tamm SA, Whitcup SM, Gery I, et al. Immune response to retinal antigens in patients with gyrate atrophy and other hereditary retinal dystrophies. Ocul Immunol Inflamm 2001;9:75-84.

Margaret M. DeAngelis, PhD

From the Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, MA.

Reprint requests to Margaret M. DeAngelis, PhD, Harvard Medical School, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, 243 Charles Street, Boston, MA 02114. Email:

Accepted June 6, 2006.
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Author:DeAngelis, Margaret M.
Publication:Southern Medical Journal
Article Type:Editorial
Geographic Code:1USA
Date:Sep 1, 2006
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