Cross N C, Tolan D R, Cox T M
Royal Postgraduate Medical School, London, England.
Cell. 1988 Jun 17;53(6):881-5. doi: 10.1016/s0092-8674(88)90349-2.
Hereditary fructose intolerance (HFI) is a human autosomal recessive disease caused by a deficiency of aldolase B that results in an inability to metabolize fructose and related sugars. We report here the first identification of a molecular lesion in the aldolase B gene of an affected individual whose defective protein has previously been characterized. The mutation is a G----C transversion in exon 5 that creates a new recognition site for the restriction enzyme Ahall and results in an amino acid substitution (Ala----Pro) at position 149 of the protein within a region critical for substrate binding. Utilizing this novel restriction site and the polymerase chain reaction, the patient was shown to be homozygous for the mutation. Three other HFI patients from pedigrees unrelated to this individual were found to have the same mutation: two were homozygous and one was heterozygous. We suggest that this genetic lesion is a prevailing cause of hereditary fructose intolerance.
遗传性果糖不耐受症（HFI）是一种人类常染色体隐性疾病，由醛缩酶B缺乏引起，导致无法代谢果糖及相关糖类。我们在此报告首次在一名受影响个体的醛缩酶B基因中鉴定出分子病变，其缺陷蛋白此前已得到表征。该突变是外显子5中的G→C颠换，为限制性酶Ahall创造了一个新的识别位点，并导致蛋白质第149位氨基酸发生取代（丙氨酸→脯氨酸），该区域对底物结合至关重要。利用这个新的限制性位点和聚合酶链反应，该患者被证明为该突变的纯合子。在与该个体无关的家系中的另外三名HFI患者被发现具有相同的突变：两名是纯合子，一名是杂合子。我们认为这种基因病变是遗传性果糖不耐受症的主要病因。
