Lysinuric protein intolerance (LPI; OMIM 222700) is a rare, recessive disorder with a worldwide distribution, but with a high prevalence in the Finnish population; symptoms include failure to thrive, growth retardation, muscle hypotonia and hepatosplenomegaly. A defect in the plasma membrane transport of dibasic amino acids has been demonstrated at the baso-lateral membrane of epithelial cells in small intestine and in renal tubules and in plasma membrane of cultured skin fibroblasts from LPI patients. The gene causing LPI has been assigned by linkage analysis to 14q11-13. Here we report mutations in SLC7A7 cDNA (encoding y+L amino acid transporter-1, y+LAT-1), which expresses dibasic amino-acid transport activity and is located in the LPI region, in 31 Finnish LPI patients and 1 Spanish patient. The Finnish patients are homozygous for a founder missense mutation leading to a premature stop codon. The Spanish patient is a compound heterozygote with a missense mutation in one allele and a frameshift mutation in the other. The frameshift mutation generates a premature stop codon, eliminating the last one-third of the protein. The missense mutation abolishes y+LAT-1 amino-acid transport activity when co-expressed with the heavy chain of the cell-surface antigen 4F2 (4F2hc, also known as CD98) in Xenopus laevis oocytes. Our data establish that mutations in SLC7A7 cause LPI.

Omega-3 LC-PUFA dietary supplement during pregnancy and lactation influenced the mother and newborn's fatty acid profile and nervonic acid content but did not show effects on visual and cognitive/psychomotor development.

The aim of the study was to assess the fatty acid composition of human fertilization-failed oocytes. A total of 150 unfertilized oocytes from 43 women undergoing in-vitro fertilization (IVF) were analysed using capillary gas chromatography. The majority of fatty acids were saturated (79.22%), of which stearic (38.65%) and palmitic (32.66%) acids were the most abundant. Of the monounsaturated fatty acids (14.27%) oleic acid was the most abundant (9.77%). Polyunsaturated fatty acids comprised 6.50% of fatty acids, the n-6:n-3 ratio being 7.73. The ratio of eicosapentaenoic acid:docosahexaenoic acid was approximately 5. It is concluded that the most common fatty acids in human unfertilized oocytes are either saturated or monounsaturated fatty acids, whose main function is to provide an energy source. A number of differences in fatty acid composition were observed, in comparison with other biological samples. In particular, stearic and eicosapentaenoic acids were more prominent, and oleic and linoleic acids were less prominent; this may reflect some specific peculiarity of oocyte metabolism.

We present an extensive study of the genetic diversity of phenylalanine hydroxylase deficiency in the Spanish phenylketonuria population. We have analysed 195 PKU patients by DGGE analysis identifying 67 different mutations which represent 89% of the total mutant chromosomes. Seventeen mutations first described in Spain have not yet been detected elsewhere; ten of these are reported here for the first time. The clinical significance of this high genetic heterogeneity was examined by analysing the genotype-phenotype correlations, mainly focusing on the mild hyperphenylalaninaemia (MHP) phenotype. The genotypes found in a group of 93 MHP patients, the largest analysed so far, are described in detail, as well as the relative frequencies of the MHP mutations identified. From the total pool of mutations, 27 can be considered severe, 18 can be defined as mild and 13 as associated with MHP. The prevalent mutations correspond to one severe mutation (IVS10nt-11), one MHP mutation (A403V) and two mild mutations (I65T and V388M). The high frequency of mutations with a low degree of severity can explain the relatively higher prevalence of MHP and mild PKU phenotypes in Spain compared with Northern European populations. We have looked at the geographical distribution in Spain of the more common mutations, finding evidence of local mutation clustering, which could be the result of differences in the ethnic background and/or of genetic drift within each region.