Epidermolysis bullosa simplex Dowling-Meara (MIM# 1317600) is the most severe of the three common epidermolysis bullosa simplex subtypes. In addition to the palmoplantar distribution seen in other epidermolysis bullosa simplex subtypes, extensive herpetiform blistering spontaneously develops on the trunk and limbs and may lead to scarring or milia formation. The keratin 5 and keratin 14 genes encode proteins that form the primary structural components of the basal epidermal keratinocytes, mutations in either of these genes can cause epidermolysis bullosa simplex. In this study we sequenced these genes in a family with epidermolysis bullosa simplex Dowling-Meara. We report a novel T to C transition in the helix termination peptide of K5 that causes a nonconservative substitution of a highly conserved amino acid within this critical region (I466T). This mutation adds to those previously reported and provides further evidence of phenotype-genotype correlation in epidermolysis bullosa simplex.

Docosahexaenoic acid (DHA) is an integral component of neural cell membranes and is critical to the development and function of the CNS. A premature delivery interrupts normal placental supply of DHA such that the infant is dependent on the nature of the nutritional support offered. The most abundant omega-3 fatty acid in pre-term formulas is ␣ linolenic acid (ALNA), the precursor of DHA. This project studied the absorption, ␤-oxidation and conversion of ALNA to DHA by pre-term infants ranging from 30-37 wk of corrected gestation. [U-13 C] ALNA was administered emulsified with a pre-term formula to 20 well pre-term infants on full enteral feeds. Enrichment of 13 C in stool and as 13 CO 2 in breath was used to estimate absorption across the gut and partitioning toward ␤-oxidation respectively. Excretion of the administered dose of 13 C in stool ranged from 2.0 to 26.2%; excretion decreased with increasing birth gestation. Appearance as 13 CO 2 on breath ranged from 7.6 to 19.0%. All infants synthesised eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA) and DHA with the least mature having the highest cumulative plasma DHA. These results show considerable variation suggesting that the worst absorption of ALNA and the greatest production of DHA occur in infants born at the earliest gestation.

Linkage and association has been reported between CTLA4 DNA markers and susceptibility to type 1 diabetes in some populations, but not others. We performed case-control and family-based association studies to assess if the CTLA4 A49G and intron 1 C/T polymorphisms were associated with development of early onset type 1 diabetes in the Northern Ireland population. The distribution of A49G and C/T alleles in cases (n = 144) was similar to those observed in controls (n = 307). In contrast, significant distortions in allele transmissions from informative parents to probands were observed for both the A49G (P = 0.02) and C/T (P = 0.01) polymorphisms employing 297 nuclear families. Our results suggest that the CTLA4 gene may play a minor role in the overall genetic predisposition to type 1 diabetes in this UK population.

Background/Objectives: The role of individual fatty acids in the development of cardiovascular disease (CVD) is well established, but the effects of an overall pattern of fatty acids in CVD risk has yet to be elucidated. Circulating fatty acid levels are related to metabolic disturbances associated with the metabolic syndrome and CVD, due to disturbances in the activity of enzymes that catalyse fatty acid desaturation (D-desaturases). Therefore, we determined patterns of fatty acids and estimated desaturase activity in plasma and analysed how these patterns were related to a 10-year CVD risk estimates in a middle-aged male population in Northern Ireland. Subjects/Methods: Principal components analysis (PCA) was performed for defining fatty acid patterns in 379 men aged 30-49 years. Logistic regression analyses were then carried out for analysing the relationship between these fatty acid patterns and the 10-year CVD risk estimates. Results: The PCA generated three high fatty acid patterns: high saturated fatty acid (SFA), high omega 3 fatty acid (omega 3) and high monosaturated fatty acid (MNFA). Results from logistic regression analyses show that a 1 s.d. increase in the SFA pattern score was significantly and positively associated with an increase in the 10-year CVD risk category (odds ratio 1.71, 95% confidence interval 1.33-2.21, Po0.0001) even after adjustment for lifestyle factors. There were no significant relationships between the other two pattern scores and the 10-year CVD risk. Conclusions: An unhealthy fatty acid pattern representing both dietary intake and in vivo fatty acid metabolism is related to the 10-year CVD risk estimates and provide evidence that, as with dietary patterns, the synergistic effect of multiple fatty acids may be more important in relation to the development of CVD risk.

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