To examine the sensitivity of vitiligo melanocytes to external oxidative stress, we studied enzymatic and non-enzymatic anti-oxidants in cultured melanocytes of normal subjects (n = 20) and melanocytes from apparently normal skin of vitiligo patients (n = 10). The activity of superoxide dismutase and catalase and the intracellular concentrations of vitamin E and ubiquinone were evaluated in cultures at the fourth or fifth passage. In addition, cells were exposed to various concentrations of a peroxidizing agent, cumene hydroperoxide (CUH, 0.66-20 microM), for 1 and 24 h. Compared to normal melanocytes, vitiligo melanocytes showed normal superoxide dismutase and significantly lower catalase activities and higher vitamin E and lower ubiquinone levels. At the concentration used, CUH did not significantly affect cell number or viability of melanocytes after either period of culture. On the contrary, vitiligo melanocytes were susceptible to the toxic effect of CUH after 24 h of continuous treatment at concentrations greater than 6.6 microM. The degree of CUH toxicity correlated strictly with the anti-oxidant pattern, defined as the ratio between vitamin E concentration and catalase activity, suggesting that the alteration in the antioxidants was the basis for sensitivity to the external oxidative stress. Our results demonstrate the presence of an imbalance in the anti-oxidant system in vitiligo melanocytes and provide further support for a free radical-mediated damage as an initial pathogenic event in melanocyte degeneration in vitiligo.

In order to evaluate the free radical defense systems of melanocytes and their possible correlation with melanoma, we have studied in cultured normal human melanocytes (20), normal melanocytes from melanoma patients (15), and melanoma cells (40) the fatty acid pattern of membrane phospholipids as a target of peroxidative damage and the superoxide dismutase and catalase activities, vitamin E, and ubiquinone levels as intracellular antioxidants. Cells were cultured in the same medium and analyzed at III or IV passage. Compared to the values obtained in normal human melanocytes, melanoma cells showed on average: a) higher levels of polyunsaturated fatty acids, b) increased superoxide dismutase and decreased catalase activities, higher vitamin E, and lower ubiquinone levels. Among the normal melanocytes from melanoma patients studied, two groups were differentiated: a) cultures (7) with enzymatic and non-enzymatic antioxidants level similar to those of normal human melanocytes; b) cultures (8) with antioxidant patterns similar to those observed in melanoma cells. Polyunsaturated fatty acids were also increased in the latter group. The results indicate that in melanoma cells and in a percentage of normal melanocytes from melanoma patients, an imbalance in the antioxidant system can be detected that can lead to endogenous generation of reactive oxygen species and to cellular incapability of coping with exogenous peroxidative attacks. These alterations could be correlated with the malignant transformation of cells and with the progression of the disease.

Adenomatous polyposis coli (APC) is an autosomal dominant disease characterized by the development of hundreds of colorectal adenomatous polyps during the first decades of life. The expression of the disease varies, as the age of onset of colonic cancer and the severity of extracolonic manifestations often differ between affected families. An attenuated form of APC has also been described in which a small number of polyps and a later age of onset of colonic cancer is observed. Cloning of the APC gene has allowed disease-causing mutations in APC families to be identified. Here, we report a novel splice site mutation (a G to T transversion at position +5 of the splice donor site in intron 9) in the APC gene of affected individuals in an Italian family. Characterization of the transcription products from this mutant APC allele revealed that normal splicing was disrupted: a shorter mRNA was expressed in which exon 8 was connected directly to exon 10. This created a shift in the reading frame and the introduction of a stop codon at position 1358. In addition, some normal APC transcript was produced from the mutant allele in lymphoblastoid cells. A comparison of the clinical features of affected members of this family with four unrelated Italian APC kindreds, in which the same AAAAG deletion at position 3926 has been found, showed a significant difference in the onset of disease symptoms and in the age of death attributable to colorectal cancer. Inefficient exon skipping may be, at least in part, responsible for the delay in the development of the disease in the reported family.

We report two related patients, presenting duplication 20p, with a characteristic phenotype including normal growth pattern, mental and psycho‐motor retardation, reduced motor coordination, poor language development, round face and prominent cheeks, vertebral and dental anomalies, and renal malformations. Familial chromosome analysis showed a balanced translocation t(20;21)(pll;q22) in three members of the family. These cases, together with those previously reported in the literature, allow us to make a better delineation of the duplication 20p syndrome, identifying more clearly the symptoms that must be considered as characteristic of this clinical picture.

Congenital bilateral microphthalmos is a rare malformation ofthe eye, which ranges from extreme to mild reduction of total axial length. Microphthalmos may occur as an isolated ocular abnormality or as part of a systemic disorder, and different classifications of the condition have been attempted.We describe a large pedigree with 14 persons in four generations affected with bilateral microphthlamos without other ocular or systemic signs. An autosomal dominant trait with complete penetrance is proposed. Five subjects underwent a complete ophthalmological evaluation. The total axial length was measured by A scan ultrasonography in all persons. Ultrasonography showed a reduction of the total axial length (range 18-4-19-7 mm) and a reduced vitreous cavity length (range 11-4-13 5 mm) in all investigated patients. All the patients had microcornea (range 8-9-7 mm). No other ocular anomalies or associated systemic malformations were found.A review of published reports also suggests that simple, partial, posterior, pure microphthalmos and nanophthalmos are similar clinical entities sharing total axial length and vitreous cavity length reduction. Therefore, the term simple microphthalmos is proposed to identify these clinical conditions.

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