Six novel alleles identified in Italian hereditary fructose intolerance patients enlarge the mutation spectrum of the aldolase B gene.
Hereditary fructose intolerance (HFI) is a recessively inherited disorder of carbohydrate metabolism caused by impaired functioning of human liver aldolase (B isoform; ALDOB). To-date, 29 enzyme-impairing mutations have been identified in the aldolase B gene. Here we report six novel HFI single nucleotide changes identified by sequence analysis in the aldolase B gene. Three of these are missense mutations (g.6846T>C, g.10236G>T, g.10258T>C), one is a nonsense mutation (g.8187C>T) and two affect splicing sites (g.8180G>C and g.10196A>G). We have expressed in bacterial cells the recombinant proteins corresponding to the g.6846T>C (p.I74T), g.10236G>T (p.V222F), and g.10258T>C (p.L229P) natural mutants to study their effect on aldolase B function and structure. All the new variants were insoluble; molecular graphics data suggest this is due to impaired folding.
Esposito
Gabriella
G
Dipartimento di Biochimica e Biotecnologie Mediche, Università di Napoli Federico I, Italy.
Santamaria
Rita
R
Vitagliano
Luigi
L
Ieno
Luigi
L
Viola
Antonietta
A
Fiori
Laura
L
Parenti
Giancarlo
G
Zancan
Lucia
L
Zagari
Adriana
A
Salvatore
Francesco
F
D000328:Adult; D000483:Alleles; D002648:Child; D004252:DNA Mutational Analysis; D005260:Female; D005633:Fructose Intolerance / Q000201:enzymology / Q000235:genetics*; D005634:Fructose-Bisphosphate Aldolase / Q000235:genetics*; D006801:Humans; D007558:Italy; D009154:Mutation
D005634:Fructose-Bisphosphate Aldolase