Clinical and molecular spectra in galactosemic @entity1 from neonatal screening in northeastern Italy: Structural and functional characterization of new variations in the XXXX ( @entity29272 ) gene.

@entity1 @entity71420 @entity71424 @entity73 @entity71423 @entity71426 @entity71427 @entity71425 @entity29272 @entity71421 @entity2670 @entity717 @entity204 @entity1624 @entity71419 @entity71422 @entity2246
UNASSIGNED: @entity1624 is an @entity2246 due to mutations of the @entity29272 gene leading to toxic accumulation of galactose and derived metabolites. With the benefit of early diagnosis by neonatal screening and early therapy, the acute presentation of @entity1624 can be prevented. However, despite early diagnosis and treatment, the long term outcome for these @entity1 is still unpredictable because they may go on to develop @entity73 , speech problems, neurological and/or @entity717 and, in females, @entity2670 . The objectives of the current study were to report our experience with a group of galactosemic @entity1 identified through the neonatal screening programs in northeastern Italy during the last 30years. No @entity204 due to @entity1624 complications occurred after the introduction of the neonatal screening program. However, despite the early diagnosis and dietary treatment, the @entity1 with @entity1624 showed one or more long-term complications. A total of 18 different variations in the @entity29272 gene were found in the @entity1 cohort: 12 missense, 2 frameshift, 1 nonsense, 1 deletion, 1 silent variation, and 1 intronic. Six ( @entity71419 , @entity71420 , @entity71421 , @entity71422 , @entity71423 , @entity71424 ) were new variations. The most common variation was @entity71425 (12 alleles, 31.5%), followed by @entity71426 (6 alleles, 15.7%) and @entity71427 (6 alleles, 15.7%). The other variations comprised 1 or 2 alleles. In the @entity1 carrying a new mutation, the biochemical analysis of @entity29272 activity in erythrocytes showed an activity of <1%. In silico analysis (SIFT, PolyPhen-2 and the computational analysis on the static protein structure) showed potentially damaging effects of the six new variations on the @entity29272 protein, thus expanding the genetic spectrum of @entity29272 variations in Italy. The study emphasizes the difficulty in establishing a genotype-phenotype correlation in @entity1624 and underlines the importance of molecular diagnostic testing prior to making any treatment.
