Ohtsuki, Hiroshi

The purpose of this study was to search for chromosomal susceptibility loci for comitant strabismus. Genomic DNA was isolated from 10mL blood taken from each member of 30 nuclear families in which 2 or more siblings are affected by either esotropia or exotropia. A genome-wide search was performed with amplification by polymerase chain reaction of 400 markers in microsatellite regions with approximately 10 cM resolution. For each locus, non-parametric affected sib-pair analysis and non-parametric linkage analysis for multiple pedigrees (Genehunter software, http://linkage.rockefeller.edu/soft/) were used to calculate multipoint lod scores and non-parametric linkage (NPL) scores, respectively. In sib-pair analysis, lod scores showed basically flat lines with several peaks of 0.25 on all chromosomes. In non-parametric linkage analysis for multiple pedigrees, NPL scores showed one peak as high as 1.34 on chromosomes 1, 2, 4, 7, 10, 15, and 16, while 2 such peaks were found on chromosomes 3, 9, 11, 12, 18, and 20. Non-parametric linkage analysis for multiple pedigrees of 30 families with comitant strabismus suggested a number of chromosomal susceptibility loci. Our ongoing study involving a larger number of families will refine the accuracy of statistical analysis to pinpoint susceptibility loci for comitant strabismus.</P>

The purpose of this study was to elucidate the role of extracellular matrix components such as aggrecan, fibronectin, and laminin in the extraocular muscle of patients with strabismus. Resected tissues of the medial rectus muscle of 47 patients with intermittent exotropia obtained during recession-resection surgery were frozen under liquid nitrogen and pulverized by a Freezer/Mill to solubilize the tissue for enzyme immunoassay. The total amounts of aggrecan, fibronectin, and laminin in the resected tissue were correlated with clinical data of patients such as age, exodeviation, and refractive error. The amount of aggrecan decreased significantly with the advance of age (P < 0.0001, Spearman rank correlation test), while the amount of laminin or fibronectin had no correlation with age. Patients with basic type intermittent exotropia showed larger, although not significantly, amounts of aggrecan than those with convergence insufficiency type (P = 0.0538, Mann-Whitney U-test). The amount of aggrecan may be related to motor aspects of intermittent exotropia.

To identify ARIX gene and PHOX2B gene polymorphisms in patients with congenital superior oblique muscle palsy, 3 exons of the ARIX gene and PHOX2B gene were sequenced by genomic DNA amplification with polymerase chain reaction (PCR) and direct sequencing in 31 patients with congenital superior oblique muscle palsy and in 54 normal individuals. A family with a father and one daughter each having congenital superior oblique muscle palsy was also included in this study. Eleven patients with congenital superior oblique muscle palsy had heterozygous nucleotide changes in the ARIX gene, including 4 patients reported on previously. One patient with atrophy of the superior oblique muscle had a new change of T-4G in the promoter region of the ARIX gene. The other 6 patients had a heterozygous nucleotide change of G153A in the 5'-untranslated region (UTR) of the exon 1 of the ARIX gene. These nucleotide changes of the ARIX gene, taken together, had a significant association with congenital superior oblique muscle palsy(P = 0.0022). One patient and 5 patients had heterozygous nucleotide changes of A1106 C and A1121 C in exon 3 of the PHOX2B gene, respectively, while these changes were absent in the normal individuals. Two patients had both the G153A change in the 5'-UTR of exon 1 of the ARIX gene and the A1121 C change in exon 3 of the PHOX2B gene. In conclusion, the polymorphisms of the ARIX gene and PHOX2B gene may be genetic risk factors for the development of congenital superior oblique muscle palsy.

We herein determined by fluorescence in situ hybridization the chromosomal localization of 2 human genes, BRAL1 and BCAN, both of which belong to the link-module superfamily, i.e. to the same band of chromosome 1q21-23. Further analysis of the genomic organization of BRAL1 and BCAN revealed that the BRAL1 gene was located 20-kb upstream of the BCAN start site. We isolated a polymorphic dinucleotide (CA) repeat sequence from a genomic clone containing the BCAN gene. High heterozygosity (0.79) makes this polymorphism a useful marker in the study of genetic disorders. Knowledge of the structure of the genes and the marker provides essential information for further analysis of the gene locus at chromosome 1q21-23.

We analyzed nucleotide changes in 3 genes, ARIX, PHOX2B, and KIF21A, in 6 patients of 3 families with congenital superior oblique muscle palsy. Three exons of ARIX, 3 exons of PHOX2B, and exons 8, 20, and 21 of KIF21A were amplified by polymerase chain reaction from genomic DNA isolated from the peripheral blood. The DNA fragments were directly sequenced in both directions. In 2 different families, a heterozygous nucleotide change, ARIX 153G>A, in the 5’-untranslated region was found in common between a father and daughter with muscle palsy and between a mother and daughter with muscle palsy (Family No. 1 and No. 3). In the other family (Family No. 2), a heterozygous 15-nucleotide deletion, PHOX2B 1124del15, resulting in loss of 5 alanine residues in the alanine repeat of the protein, was found in the daughter with muscle palsy and her father with normal traits, but was not found in the mother with muscle palsy. No KIF21A nucleotide change was found in any patients. The ARIX 153G>A polymorphism might be a genetic risk factor for the development of congenital superior oblique muscle palsy.

The aim of this study is to clarify visual symptoms and compliance with spectacle wear in children kusing progressive addition lenses (PALs). Ninety-two children, participating in a randomized, doublemasked, crossover trial to determine whether PALs reduce myopia progression (mean+/-SD age: 11.0+/-1.6 years; refractive errors: 3.11+/-1.34 D), wore PALs (1.50 D near addition) or single vision lenses (SVLs) for 18 months, alternately. A questionnaire survey was performed 6 and 12 months after the beginning of the use of the lenses (6-month survey), and the results were compared between PAL- and SVL-wearing periods. In the PAL-wearing period, the children reported difficulty in adapting to newly provided spectacles (36%), disturbances in distance vision (22%), vertigo in the lateral gaze (11%), and difficulty in ascending and descending stairs (9%). However, the frequency of these symptoms was not significantly different from that reported in the SVL-wearing period. There was no difference in compliance with spectacle wear between the PAL- and SVL-wearing periods, and 98% of the children wearing PALs reported excellent compliance. The results of this study indicate that, compared with SVLs, the PALs provide a similar level of comfort and compliance with spectacle wear for myopic children.

The purposes of this study were to examine whether body sway is altered immediately after strabismus surgery in children and to find preoperative clinical factors associated with body sway. In a prospective study, body sway was measured on 1-3 days before surgery and on the third day after surgery; for the measurements, computerized static stabilometry was carried out on 28 consecutive patients with strabismus (age range: 3 to 12 years old; mean: 7.4) who underwent strabismus surgery under general anesthesia. The linear length of the sway path (cm), the linear length of the sway path in a particular unit of time (cm/second), and the area of the sway path (cm2), indicative of the extent of body sway, all increased significantly among a total of 28 patients in both conditions of the patient's eyes open and closed, as well as among those in a subgroup of 16 patients with exotropia, after they had undergone strabismus surgery (p < 0.05, Wilcoxon signed ranks test). The center of pressure along the Y axis of orientation from the toe to the heel was found to deviate significantly toward the heel postoperatively, as compared with the preoperative center in the subgroup of 16 patients with exotropia (p < 0.05). Before surgery, 15 patients with no stereoacuity exhibited a greater amount of body sway when their eyes were open than did 13 patients with measurable stereoacuity (p < 0.05, Mann-Whitney U-test). In the subgroup of 16 patients with exotropia when their eyes open, 3 patients with abnormal head posture exhibited more extensive body sway than did 13 patients without abnormal head posture (p < 0.05). Body sway was found to significantly increase immediately after strabismus surgery in children with strabismus. Stereoacuity and abnormal head posture are 2 clinical factors associated with preoperative postural instability.