The strictly regulated expression of most pleiotropic developmental control genes is critically dependent on the activity of long-range cis-regulatory elements. This was revealed by the identification of individuals with a genetic condition lacking coding-region mutations in the gene commonly associated with the disease but having a variety of nearby chromosomal abnormalities, collectively described as cis-ruption disease cases. The congenital eye malformation aniridia is caused by haploinsufficiency of the developmental regulator PAX6. We discovered a de novo point mutation in an ultraconserved cis-element located 150 kb downstream from PAX6 in an affected individual with intact coding region and chromosomal locus. The element SIMO acts as a strong enhancer in developing ocular structures. The mutation disrupts an autoregulatory PAX6 binding site, causing loss of enhancer activity, resulting in defective maintenance of PAX6 expression. These findings reveal a distinct regulatory mechanism for genetic disease by disruption of an autoregulatory feedback loop critical for maintenance of gene expression through development.

IFX and ADA appear to be effective and safe for treatment of refractory JIA-related uveitis, with a better performance of ADA in the medium-term period.

Improved health-related quality of life (HRQOL) and reduced activity limitations are prime objectives of migraine therapy, but no data on the effect of preventive treatments on these outcomes are available. We monitored changes in HRQOL using the Short Form 36 (SF-36) and headache-related activity limitations using the Migraine Disability Assessment Score (MIDAS) in 141 consecutive migraine without aura patients on prophylaxis. A total of 102 patients completed the 3-month study. Mean (SD) number of headache days/month dropped from 8.0 (3.7) to 5.0 (2.3) (P < 0.001). Mean monthly consumption of acute drugs reduced from 7.4 (3.5) to 4.4 (3.1) (P < 0.001). MIDAS total score reduced (improved) significantly. All SF-36 scale scores increased (improved), most significantly. This first study to assess prospectively the impact of prophylaxis on HRQOL and daily activities in a large series indicates that migraine prophylaxis has the potential to reduce the global burden of migraine on individuals and society.

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Bone marrow transplantation (BMT) is recognized as a successful treatment for malignant and non-malignant hematological diseases. Thanks to transplantation, the number of long-term survivors has risen and with the improved prognosis a problem of ocular side effects has arisen. We carried out a retrospective study to determine the incidence and etiopathogenesis of ocular complications in a series of young patients undergoing BMT. One hundred children (62 males and 38 females) with a mean age of 7.12 (±3.3) years at the time of BMT (autologous in 66 cases, allogenic in 34) were followed for a mean of 4.2 years (range 2–9). The conditioning regimens preceding BMT induced cytoreductive chemotherapy alone (47 cases) or associated with total body irradiation (TBI) (53 cases) in three or six fractions for a total dose of 10–12 Gy. We examined every child before BMT and subsequently every six months. We did not include patients with ocular complications due to the primary disease. Thirty-three children showed several complications after BMT: 17 had subcapsular posterior cataract in both eyes and eight had tear hyposecretion; one had dramatic fungal panuveitis, four had hemorrhagic complications and five optic disk edema. TBI was significantly associated with the development of subcapsular posterior cataract.