Rubinstein-Taybi syndrome (RSTS) is a heterogeneous disorder with approximately 45-55% of patients showing mutations in the CREB binding protein and a further 3% of patients having mutations in EP300. We report a male child with a deletion of exons 3-8 of the EP300 gene who has RSTS. He has a milder skeletal phenotype, a finding that has been described in other cases with EP300 mutations. The mother suffered from pre-eclampsia and HELLP syndrome in the pregnancy. She subsequently developed a mullerian tumor of her cervix 6 years after the birth of her son.

Classical galactosaemia (OMIM #230400), a rare disorder of carbohydrate metabolism, is caused by a deficient activity of galactose-1-phosphate uridyltransferase (EC 2.7.7.12). The pathophysiology of the long-term complications, mainly cognitive, neurological and female fertility problems remains poorly understood. The lack of validated biomarkers to determine prognosis, monitor disease progression and responses to new therapies, pose a huge challenge. We report the detailed analysis of an automated robotic hydrophilic interaction ultra-performance liquid chromatography N-glycan analytical method of high glycan peak resolution applied to serum IgG. This has revealed specific N-glycan processing defects observed in 40 adult galactosaemia patients (adults and adolescents), in comparison with 81 matched healthy controls. We have identified a significant increase in core fucosylated neutral glycans (Po0.0001) and a significant decrease in core fucosylated (Po0.001), non-fucosylated (Po0.0001) bisected glycans and, of specific note, decreased N-linked mannose-5 glycans (Po0.0001), in galactosaemia patients. We also report the abnormal expression of a number of related relevant N-glycan biosynthesis genes in peripheral blood mononuclear cells from 32 adult galactosaemia patients. We have noted significant dysregulation of two key N-glycan biosynthesis genes: ALG9 upregulated (Po0.001) and MGAT1 downregulated (Po0.01) in galactosaemia patients, which may contribute to its ongoing pathophysiology. Our data suggest that the use of IgG N-glycosylation analysis with matched N-glycan biosynthesis gene profiles may provide useful biomarkers for monitoring response to therapy and interventions. They also indicate potential gene modifying steps in this N-glycan biosynthesis pathway, of relevance to galactosaemia and related N-glycan biosynthesis disorders.

Abstract. Selection for late-life fecundity and longevity in adult Drosophila melanogaster is well known to modify numerous characteristics of life history and physiology. We report experiments here in which selection applied to behavior affects features in an identical fashion. Selection for feeding rate of larval D. melanogaster modifies caloric intake, as measured by the uptake and incorporation of labeled glucose. Selection for slow larval feeding produced lines of D. melanogaster in which larvae synthesized significantly less lipid prior to pupation and eclosed to have low early-life fecundity and a long life as adults. They also had greater lifetime fecundity, but lower viability of egg to hatched adult. Alternatively, fast-feeding larvae incorporated more lipid before pupation and eclosed with high earlyfecundity that declined rapidly throughout their short adult life. Slow-feeding populations also had a significantly enhanced expression of the stress-resistance genes CuZn-SOD, CATALASE, and HSP70. Selection on larval feeding behavior reproduced the antagonistic evolutionary trade-off found under selection for adult life span and mimicked the physiological response in life span as seen in many species when dietary restriction is imposed on adults. Thus, nutrient acquisition during development appears to share a common evolutionary and genetic basis with the allocation processes that determine adult life-history traits and the related phenotypic dietary restriction phenomena.

A case of Jacobsen syndrome, suspected antenatally on the grounds of trigonocephaly and hypoplastic left heart syndrome, is presented. Clinicians are reminded that a hypoplastic left heart should not be assumed to be an isolated malformation and that a careful search for associated malformations can facilitate the recognition of an underlying genetic syndrome.