Six Novel Alleles Identified in Italian Hereditary Fructose Intolerance Patients Enlarge the Mutation Spectrum of the Aldolase B Gene

被引：20

作者：

Esposito, Gabriella ^{[1
,2
]}

Santamaria, Rita ^{[1
,2
,8
]}

Vitagliano, Luigi ^{[3
,4
]}

Ieno, Luigi ^{[1
,2
]}

Viola, Antonietta ^{[1
,2
]}

Fiori, Laura ^{[5
]}

Parenti, Giancarlo ^{[6
]}

Zancan, Lucia ^{[7
]}

Zagari, Adriana ^{[2
,3
,4
]}

Salvatore, Francesco ^{[1
,2
]}

机构：

[1] Univ Napoli Federico I, Dipartimento Biochim & Biotecnol Med, Naples, Italy

[2] CEINGE Biotecnol Avanzate, Naples, Italy

[3] CNR, Ist Biostrutture & Bioimmagini, Naples, Italy

[4] Univ Napoli Federico I, Dipartimento Chim Biol, Naples, Italy

[5] Univ Milan, Ist Clin Perfezionamento, Milan, Italy

[6] Univ Napoli Federico I, Dipartimento Clin Pediat Gen & Specialist, Naples, Italy

[7] Univ Padua, Dipartimento Pediat, Padua, Italy

[8] Univ Napoli Federico, Dipartimento Farmacol Sperimentale, Naples, Italy

来源：

HUMAN MUTATION | 2004年 / 24卷 / 06期

关键词：

Aldolase B; ALDOB; hereditary fructose intolerance; HFI; protein expression; molecular modeling;

D O I：

10.1002/humu.9290

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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. (c) 2004 Wiley-Liss, Inc.

引用

页码：1 / 8

页数：8

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