RB1 mutation spectrum in a comprehensive nationwide cohort of retinoblastoma patients.

BACKGROUND: Retinoblastoma (Rb) is a childhood cancer of the retina, commonly initiated by biallelic inactivation of the RB1 gene. Knowledge of the presence of a heritable RB1 mutation can help in risk management and reproductive decision making. We report here on RB1 mutation scanning in a unique nationwide cohort of Rb patients from the Netherlands. METHODS: From the 1173 Rb patients registered in the Dutch National Retinoblastoma Register until January 2013, 529 patients from 433 unrelated families could be included. RB1 mutation scanning was performed with different detection methods, depending on the time period. RESULTS: Our mutation detection methods revealed RB1 mutations in 92% of bilateral and/or familial Rb patients and in 10% of non-familial unilateral cases. Overall an RB1 germline mutation was detected in 187 (43%) of 433 Rb families, including 33 novel mutations. The distribution of the type of mutation was 37% nonsense, 20% frameshift, 21% splice, 9% large indel, 5% missense, 7% chromosomal deletions and 1% promoter. Ten per cent of patients were mosaic for the RB1 mutation. Six three-generation families with incomplete penetrance RB1 mutations were found. We found evidence that two variants, previously described as pathogenic RB1 mutations, are likely to be neutral variants. CONCLUSIONS: The frequency of the type of mutations in the RB1 gene in our unbiased national cohort is the same as the mutation spectrum described worldwide. Furthermore, our RB1 mutation detection regimen achieves a high scanning sensitivity.

Corneal injury threshold in rabbits for the 1540 nm infrared laser.

BACKGROUND: In the 40 yr since lasers were invented, they have become commonplace in military operations, and while their utility in this setting is undeniable, they also represent a potential hazard for those in contact with them. This threat must be recognized, information must be gathered to understand this injury potential, and the necessary measures must be taken to properly protect those who will work, train, and fight with these systems. The exact mechanisms of laser/tissue interaction at 1540 nm are not well understood. Previous studies and textbooks show remarkable disparity in reporting where 1540 nm laser energy is deposited and the quantity of energy required to cause tissue damage. Rabbit cornea is very similar histologically to that of humans with the exception that it lacks Bowman's membrane. This model has been recommended as a reasonable approximation by past researchers and avoids the use of valuable non-human, primate research animals. METHODS: A rabbit model was used to demonstrate the ability of the 1540 nm laser to produce corneal injuries. Various energies were applied to find the threshold at which injury is consistently produced. Observations included the appearance of the injury in the rabbit cornea. All rabbits were between 5 and 6 kg. RESULTS: Corneal injury was consistent at energies above 56 J x cm(-2). Injuries involved the deeper corneal stroma rather than only the epithelial layer, thus raising concern for permanent visual disability in those affected. The gross appearance of these injuries was white opaque areas easily seen within the corneal stroma. CONCLUSIONS: Data shows conclusively that the 1540 nm laser causes significant corneal damage at reproducible energy levels. Further research is clearly necessary to advance our understanding of the role of Bowman's membrane, the healing properties of the injured cornea, and the epidemiology of laser injury.