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Six novel alleles identified in Italian hereditary fructose intolerance patients enlarge the mutation spectrum of the aldolase B gene
Author(s) -
Esposito Gabriella,
Santamaria Rita,
Vitagliano Luigi,
Ieno Luigi,
Viola Antonietta,
Fiori Laura,
Parenti Giancarlo,
Zancan Lucia,
Zagari Adriana,
Salvatore Francesco
Publication year - 2004
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.9290
Subject(s) - aldolase a , biology , aldolase b , missense mutation , genetics , nonsense mutation , gene , mutant , fructose bisphosphate aldolase , mutation , rna splicing , allele , microbiology and biotechnology , biochemistry , enzyme , rna
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. © 2004 Wiley‐Liss, Inc.