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This letter is in reference to the recent article by Zito et al.
very interesting article presents evidence for the association
between a frameshift mutation (845-846delTG) in exon 8 of the
RPGR gene and an X-linked syndrome inclusive of retinitis
pigmentosa, impaired hearing and sino-respiratory infections.
We would like to take this opportunity to draw the readers’...
We would like to take this opportunity to draw the readers’
attention to our companion paper, forthcoming in the November
issue of the Journal of Medical Genetics, in which we provide
evidence for an American family with an identical phenotype
associated with a missense mutation (G173R) in the RPGR gene.
In our work, we corroborate the clinical conclusion of a plausible
association between this newly characterized syndrome and
defects in RPGR function reached by Zito et al. and our group
by providing immunohistochemical evidence that not only RPGR is
expressed in the human retina, but also along the luminal side of
the epithelial lining of human bronchi and sinuses, and at several
locations within the human and monkey cochlea. The latter
pattern of expression is consistent with the possibility that defective
RPGR function could lead to hearing loss independently of
recurrent otitis as a result of a sensorineural mechanism.
Indeed, the report of Zito et al. and ours  follow previous
in which either recurrent infections [3,4] or pure sensorineural
hearing loss  had been observed independently in association
with X-linked retinitis pigmentosa and RPGR gene defects. In
addition, in parallel to the work of our groups, Hong et al. have
recently provided corroboration to our human findings by
identifying expression of RPGR also in the epithelial lining of the
In summary, these novel findings provide evidence in favor of a
broader phenotypic range in association with RPGR mutations
than previously recognized and suggest an important role for
RPGR also in the respiratory tract and in the cochlea. Even when a
history of infections is present, the observed clinical phenotype
can be easily confused with that of Usher syndrome and, in some
cases, can be indistinguishable from it. The counseling
implications of an incorrect diagnosis of Usher syndrome, which is
transmitted as an autosomal recessive trait, are immediately
evident. Diagnosing this newly recognized clinical entity of X-
linked pseudo-Usher syndrome will require a high degree of
awareness and a high index of suspicion by ophthalmologists,
geneticists, otolaryngologists, and pediatricians alike.
(1) Zito I, Downes SM, Patel RJ, Cheetham ME, Ebenezer ND,
Jenkins SA, Bhattacharya SS, Webster AR, Holder GE, Bird AC,
Bamiou DE, and Hardcastle AJ. RPGR mutation associated with
retinitis pigmentosa, impaired hearing, and sinorespiratory
infections. J Med Genet 2003;40:609-615.
(2) Iannaccone A, Breuer DK, Wang XF, Kuo SF, Normando EM,
Filippova E, Baldi A, Hiriyanna S, MacDonald CB, Baldi F,
Cosgrove D, Morton CC, Swaroop A, Jablonski MM. Clinical and
immunohistochemical evidence for an X-linked retinitis
pigmentosa syndrome with recurrent infections and hearing loss in
association with an RPGR mutation. J Med Genet 2003; 40 (in press).
(3) van Dorp DB, Wright AF, Carothers AD, Bleecker-Wagemakers
EM. A family with RP3 type of X-linked retinitis pigmentosa: an
association with ciliary abnormalities. Hum Genet 1992;88:331-4.
(4) Dry KL, Manson FDC, Lennon A, Bergen AAB, van Dorp DB,
Wright AF. Identification of a 5'splice site mutation in the RPGR
gne in a family with X-linked retinitis pigmentosa (RP3). Hum Mutat
(5) Rosenberg T, Haim M, Hauch A-M, Parving A. The prevalence
of Usher syndrome and other retinal dystrophy-hearing impairment
associations. Clin Genet 1997;51:314-21.
(6) Hong D-H, Pawlyk B, Sokolov M, Strissel KJ, Yang J, Tulloch B,
Wright AF, Arshavsky VY, Li T. RPGR isoforms in photoreceptor
connecting cilia and the transitional zone of motile cilia. Invest Ophthalmol Vis Sci 2003;44:2413–21.