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In this study, the relationship between the fluctuation in blood oxygen and carbon dioxide tension and the progression of acute retinopathy of prematurity (ROP) was evaluated. Eighteen extremely premature infants were selected on the basis of the following criteria: gestational age less than 26 weeks, oxygen supply or mechanical ventilation for more than 50 days, transcutaneous oxygen pressure (TcPO2) recorded almost once per hour, and arterial oxygen pressure (PaO2) and arterial carbon dioxide pressure (PaCO2) measured intermittently, for over 8 weeks after birth. All of these infants developed ROP, which ceased progressing in 7 infants (group I, stage 1 or 2 ROP, international classification), but advanced in 11 (group II, stage 3 or 3+). The fluctuations in TcPO2, PaO2, and PaCO2 are represented as coefficients of both variation (CV) and mean difference (D) in these two groups. The results demonstrate that both the CV and D values of TcPO2 are significantly elevated in group II infants compared with group I infants, in the first and second 3-weeks periods, and over the entire 9-week period after birth. The incidences of extreme hyperoxemia (TcPO2 > or = 100 mm Hg) and hypoxemia (TcPO2 < 30 mm Hg) in recorded TcPO2 time series show no significant differences between these two groups. We conclude that extremely premature infants with widely fluctuating arterial oxygen tension may have a greater chance of developing progressive ROP.

Coloboma and various ocular abnormalities have been described in CHARGE syndrome, although the severity of visual impairment varies from case to case. We conducted a multicenter study to clarify the ophthalmic features of patients with molecularly confirmed CHARGE syndrome. Thirty-eight eyes in 19 patients with CHARGE syndrome and confirmed CHD7 mutations treated at four centers were retrospectively studied. Colobomata affected the posterior segment of 35 eyes in 18 patients. Both retinochoroidal and optic disk colobomata were bilaterally observed in 15 patients and unilaterally observed in 3 patients. The coloboma involved the macula totally or partially in 21 eyes of 13 patients. We confirmed that bilateral large retinochoroidal colobomata represents a typical ophthalmic feature of CHARGE syndrome in patients with confirmed CHD7 mutations; however, even eyes with large colobomata can form maculas. The anatomical severity of the eye defect was graded according to the presence of colobomata, macula defect, and microphthalmos. A comparison of the severity in one eye with that in the other eye revealed a low-to-moderate degree of agreement between the two eyes, reflecting the general facial asymmetry of patients with CHARGE syndrome. The location of protein truncation and the anatomical severity of the eyes were significantly correlated. We suggested that the early diagnosis of retinal morphology and function may be beneficial to patients, since such attention may determine whether treatment for amblyopia, such as optical correction and patching, will be effective in facilitating the visual potential or whether care for poor vision will be needed.

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We performed array comparative genomic hybridization utilizing a whole genome oligonucleotide microarray in a patient with the autism spectrum disorders (ASDs) and persistent hyperplastic primary vitreous (PHPV). Submicroscopic deletions in 7q31 encompassing CADPS2 (Ca(2+) -dependent activator protein for secretion 2) and TSPAN12 (one of the members of the tetraspanin superfamily) were confirmed. The CADPS2 plays important roles in the release of neurotrophin-3 and brain-derived neurotrophic factor. Mutations in TSPAN12 are a relatively frequent cause of familial exudative vitreoretinopathy. We speculate that haploinsufficiency of CADPS2 and TSPAN12 contributes to ASDs and PHPV, respectively.

Deep intronic mutations are often ignored as possible causes of human disease. Using whole-exome sequencing, we analysed genomic DNAs of a Japanese family with two male siblings affected by ocular albinism and congenital nystagmus. Although mutations or copy number alterations of coding regions were not identified in candidate genes, the novel intronic mutation c.659-131 T > G within GPR143 intron 5 was identified as hemizygous in affected siblings and as heterozygous in the unaffected mother. This mutation was predicted to create a cryptic splice donor site within intron 5 and activate a cryptic acceptor site at 41nt upstream, causing the insertion into the coding sequence of an out-of-frame 41-bp pseudoexon with a premature stop codon in the aberrant transcript, which was confirmed by minigene experiments. This result expands the mutational spectrum of GPR143 and suggests the utility of next-generation sequencing integrated with in silico and experimental analyses for improving the molecular diagnosis of this disease.