Letters to the Editor
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238 Br J Ophthalmol 2001;85:238–248 Br J Ophthalmol: first published as 10.1136/bjo.85.2.238d on 1 February 2001. Downloaded from LETTERS TO THE EDITOR DiVerent mutation of the XLRS1 gene causes juvenile retinoschisis with retinal white flecks EDITOR,—Juvenile retinoschisis is an X linked inherited vitreoretinal degeneration that re- sults in splitting of the superficial layers of the retina.1 Retinal white flecks are rarely present in retinoschisis.2 Because we have three families with retinoschisis with retinal white flecks, the clinical features and genetic analysis of both XLRS1 and RDH5 genes were investi- gated in these families to characterise this unusual fundus finding. CASE REPORT Case 1 A 17 year old young man was diagnosed as having retinoschisis at 11 months of age. We have reported some of his clinical findings at the age of 10 years.2 His maternal grandfather Figure 2 Posterior pole in the four cases. (a) Right eye of case 1. (b) Right eye of case 2. (c) Left eye of case 3. (d) Left eye of case 4. All cases showed foveal schisis. Cases 1, 3, and 4 showed retinal white flecks. and his younger brother (case 2) are also Case 4 known to have this condition (Fig 1a). Both A 22 year old man was found to have fundi showed the typical star-shaped configu- hypermetropia and was corrected by glasses at ration in the macula and peripheral retino- the age of 1 year. He was diagnosed as having schisis inferiorly with multiple small white retinoschisis and esotropia and consulted us at flecks scattered in the temporal posterior pole the age of 13 years. Pedigrees of case 4 showed (Fig 2a). Full field ERG recordings showed an X linked inheritance pattern (Fig 1b). markedly reduced scotopic response and even Although the left fundus showed the typical greater reduction in the photopic responses star-shaped configuration in the macula, the right macula showed degenerative changes. and a negative-type ERG with a single bright http://bjo.bmj.com/ flash stimulus. Corrected visual acuity at the Multiple small, white flecks were scattered in age of 17 years was right eye 20/200 with his left temporal posterior pole (Fig 2d). The S+4=C−2×160°, and left eye 20/100 with full field ERG showed a similar pattern to case S+4=C−2.5×20°. 1. Corrected visual acuity at the age of 22 years was: right eye 30/500 with S+7, and left eye 40/200 with S+5.25=C−1.75 × 90°. Case 2 Informed consent was obtained from the A 14 year old boy, a brother of case 1, was patients after an explanation of the study. found to have poor visual acuity at the age of 5 Genomic DNAs were extracted from leuco- on September 27, 2021 by guest. Protected copyright. years. He was diagnosed by us as having cytes of peripheral blood. Exons 1–6 of the retinoschisis at the age of 13 years. Both fundi XLRS1 gene and exons 2–5 of the RDH5 gene showed the typical star-shaped configuration were amplified by polymerase chain reaction in the macula and peripheral retinoschisis (PCR) using primers and condition described inferiorly without the multiple small white before.34 The PCR products were purified flecks (Fig 2b). The full field ERG showed a and directly sequenced using an automated similar pattern as in case 1. During the 6 year DNA sequencer, Model 373 (Applied Biosys- follow up, the white flecks did not appear. tems, USA). The hemizygous XLRS1 gene Corrected visual acuity at the age of 14 years mutations were recognised in all four patients was: right eye 10/20 with S+3=C−1.5×110°, as shown in Figure 1. No mutation of the and left eye 20/100 with S+4=C−1×160°. RDH5 gene was detected in exons 2–5 as well as flanking intron sequences. Figure 1 Genotype of four cases. (a, b) Case 3 Pedigrees of cases 1, 2, and 4. Solid symbols A 9 year old boy was found to have poor visual COMMENT indicate retinoschisis patients; open symbols, acuity, and was referred to us. He was Retinal flecks are sometimes observed in unaVected family members. Arrows indicate diagnosed as having retinoschisis at the age of diVerent types of retinal dystrophies.56 We proband and Xs indicate examined cases. (a) 5 years. Both fundi showed the typical III-1 and III-2 correspond to cases 1 and 2, have already reported that the retinal white respectively. (b) III-4 corresponds to case 4. Both star-shaped configuration in the macula. Mul- flecks rarely accompany retinoschisis.2 Re- pedigrees showed X linked inheritance pattern. tiple small, white flecks were scattered in the cently, a report indicated that mutations of the (c–f) Nucleotide sequences of the XLRS1 gene posterior pole of the left eye (Fig 2c). The RDH5 gene, which is highly expressed in the using sense primer in four patients with white flecks were not present in the right eye. retinal pigment epithelium, causes fundus retinoschisis. Arrows indicate the position of the The full field ERG showed a similar pattern as albipunctatus.4 To assess them at the genetic mutation. (c) Case 1, hemizygotic mutant in case 1. Visual fields showed a large scotoma (Glu72Lys). (d) Case 2, hemizygotic mutant level, we investigate both the XLRS1 and (Glu72Lys). (e) Case 3, hemizygotic mutant in the left eye. Corrected visual acuity at the RDH5 genes in four cases of retinoschisis (Glu72Lys). (f) Case 4, hemizygotic mutant age of 9 years was: right eye 10/20 with including three patients with retinal white (Arg200Cys). S+2.25=C−1×75°, and left eye 10/1000. flecks. Although we could not detect any www.bjophthalmol.com Letters 239 Br J Ophthalmol: first published as 10.1136/bjo.85.2.238d on 1 February 2001. Downloaded from mutations of the RDH5 gene, two kinds of CASE REPORT XLRS1 gene mutations, including the most A 28 year old landscape gardener presented to common mutation, were found. The muta- the Lions Eye Institute, Perth, with visual tions are presumed to be responsible for the problems and a request for assessment. On disease because no base substitution within examination, it was noted that she had marked the codons of XLRS1 gene was detected in bilateral, symmetrical, atrophic maculae (Fig over 100 alleles from normal individuals. In 1). In addition, she had marked hair thinning addition, a number of cases of retinoschisis and loss involving the entire head. Her best caused by a Glu72Lys mutation and several Figure 2 Pedigree. The family of the aVected corrected visual acuity was recorded as 6/36 in individual (P1) with the other aVected cases of retinoschisis caused by a Arg200Cys both eyes, with the right eye improving to 6/12 378 individuals in black. mutation have been reported. with pinhole. She wore a spectacle correction The clinical features, besides the white of −4.00 sphere right and −3.50 sphere left. extreme lower limit of normal in the right and flecks of the three patients, were very com- Her past history noted hair loss but not abnormal in the left eye with reduced b-waves. mon. All three cases showed hypermetropia, symptomatic visual loss as a child. She was Other tests showed a total error score on the poor corrected visual acuity, foveal schisis, and seen recurrently at the Royal Children’s Hos- Farnswoth 100 hue test of 136 right, and 176 negative ERG configuration. We believe that pital, Melbourne, for alopecia and fitting of left. Goldmann visual fields showed a right the retinal white flecks in retinoschisis may be wigs but not for vision loss. She complained of central scotoma of about 10 degrees to the a phenotypic variation because of the intra- changing vision aVecting reading and other stimulus but sparing the superonasal quadrant familial variation, unilaterality, and detection activities in her teens. The visual loss had pro- to the fixation point. The margin of the spared of the common XLRS1 gene defect. We were gressed through her teens and had become a area did not respect the vertical or horizontal able to follow case 1 for 17 years and no significant disability to function. She did not meridians. A central scotoma of 10 degrees to remarkable change in numbers, shape, and complain of night blindness. the stimulus was seen in the left with no areas size of the white flecks was observed. Because The patient also described her brother in spared. the punctate lesions in his right eye were Melbourne and a cousin in Berlin both of found in part of the inner layer, the flecks are whom had the combination of vision loss and COMMENT probably located in the neuroretina. alopecia. The relationship between aVected The identification of new, macular related, and individuals is shown in Figure 2. None of the disease related genes is sometimes helped by This study was supported in part by grants for the clinical features described in the aVected chil- strong linkage to a second disease or marker research committee on chorioretinal degenerations from the Ministry of Health and Welfare of Japan, dren were present in the parents or the grand- trait. The strong association of alopecia and and grant in aid for scientific research (Dr Miyake, parents. Although neither of the parents of the macular degeneration does not appear in the B11470363, Dr Hotta, C05807166) from Ministry aVected children, nor the grandparents, were literature. Recent identification of alopecia of Education, Science, Sports and Culture, Japan.