Hereditary fructose intolerance: frequency and spectrum mutations of the aldolase B gene in a large patients cohort from France--identification of eight new mutations.
We investigated the molecular basis of hereditary fructose intolerance (HFI) in 160 patients from 92 families by means of a PCR-based mutation screening strategy, consisting of restriction enzyme digestion and direct sequencing. Sixteen different mutations of the aldolase B (ALDOB) gene were identified in HFI patients. As in previous studies, p.A150P (64%), p.A175D (16%) and p.N335K (5%) were the most common mutated alleles, followed by p.R60X, p.A338V, c.360_363delCAAA (p.N120KfsX30), c.324G>A (p.K108K) and c.625-1G>A. Eight novel mutations were also identified in 10 families with HFI: a one-base deletion (c.146delT (p.V49GfsX27)), a small deletion (c.953del42bp), a small insertion (c.689ins TGCTAA (p.K230MfsX136)), one splice site mutation (c.112+1G>A), one nonsense mutation (c.444G>A (p.W148X)), and three missense mutations (c.170G>C (p.R57P), c.839C>A (p.A280P) and c.932T>C (p.L311P)). Our strategy allows to diagnose 75% of HFI patients using restriction enzymatic analysis and to enlarge the diagnosis to 97% of HFI patients when associated with direct sequencing.
Davit-Spraul
Anne
A
Laboratoire de Biochimie, CHU de Bicêtre, Assistance Publique-Hôpitaux de Paris, 78, rue du Général Leclerc, 94275 Le Kremlin Bicêtre Cedex, France et Université Paris XI, IFR Bicêtre, France.
Costa
Catherine
C
Laboratoire de Biochimie, CHU de Bicêtre, Assistance Publique-Hôpitaux de Paris, 78, rue du Général Leclerc, 94275 Le Kremlin Bicêtre Cedex, France et Université Paris XI, IFR Bicêtre, France.
Zater
Mokhtar
M
Laboratoire de Biochimie, CHU de Bicêtre, Assistance Publique-Hôpitaux de Paris, 78, rue du Général Leclerc, 94275 Le Kremlin Bicêtre Cedex, France et Université Paris XI, IFR Bicêtre, France.
Habes
Dalila
D
Service d'Hépatologie Pédiatrique, CHU de Bicêtre, Assistance Publique-Hôpitaux de Paris, Le Kremlin Bicêtre, France et Université Paris XI, IFR Bicêtre, France.
Berthelot
Jacques
J
Service de Génétique, CHU d'Angers, France.
Broué
Pierre
P
Hôpital d'Enfants, CHU de Toulouse, France.
Feillet
François
F
Centre de référence des Maladies Héréditaires du Métabolisme et Inserm U 724, CHU de Nancy, France.
Bernard
Olivier
O
Service d'Hépatologie Pédiatrique, CHU de Bicêtre, Assistance Publique-Hôpitaux de Paris, Le Kremlin Bicêtre, France et Université Paris XI, IFR Bicêtre, France.
Labrune
Philippe
P
Centre de référence des Maladies Héréditaires du Métabolisme Hépatique, Hôpital A.Béclère, Assistance Publique-Hôpitaux de Paris, Clamart, France et Université Paris XI, France.
Baussan
Christiane
C
Laboratoire de Biochimie, CHU de Bicêtre, Assistance Publique-Hôpitaux de Paris, 78, rue du Général Leclerc, 94275 Le Kremlin Bicêtre Cedex, France et Université Paris XI, IFR Bicêtre, France.
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002899:Chromosomes, Human, Pair 9; D015331:Cohort Studies; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D005602:France; D005633:Fructose Intolerance / Q000201:enzymology* / Q000235:genetics; D005634:Fructose-Bisphosphate Aldolase / Q000172:deficiency / Q000235:genetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009154:Mutation
D005634:Fructose-Bisphosphate Aldolase