遗传性果糖不耐受症中醛缩酶B基因的分子分析

Molecular analysis of aldolase B genes in hereditary fructose intolerance.

作者信息

Cross N C, de Franchis R, Sebastio G, Dazzo C, Tolan D R, Gregori C, Odievre M, Vidailhet M, Romano V, Mascali G

机构信息

Department of Haematology, Royal Postgraduate Medical School, London, UK.

出版信息

Lancet. 1990 Feb 10;335(8685):306-9. doi: 10.1016/0140-6736(90)90603-3.

DOI:10.1016/0140-6736(90)90603-3

PMID:1967768

Abstract

The molecular basis of hereditary fructose intolerance (HFI) was studied in 50 subjects (41 pedigrees, 82 apparently independent mutant alleles of aldolase B) by direct analysis of aldolase B genes amplified by means of the polymerase chain reaction. The mutation A149P (ala 149----pro) was found in 67% of alleles but was significantly more common in patients from northern than from southern Europe. Two other point mutations of aldolase B were identified. A174D (C----A; ala 174----asp) was found in subjects from Italy, Switzerland, and Yugoslavia (overall frequency 16%) but not in those from the United Kingdom, France, or the United States. L288 delta C carried a single base-pair deletion causing frameshift at codon 288 and was restricted to Sicilian subjects. By testing for these mutations in amplified DNA with a limited panel of allele-specific oligonucleotides, more than 95% of HFI patients will be susceptible to genetic diagnosis.

摘要

通过聚合酶链反应扩增醛缩酶B基因并进行直接分析，对50名受试者（41个家系，82个明显独立的醛缩酶B突变等位基因）进行遗传性果糖不耐受（HFI）分子基础的研究。在67%的等位基因中发现了A149P突变（丙氨酸149→脯氨酸），但在北欧患者中比在南欧患者中更为常见。还鉴定出醛缩酶B的另外两个点突变。A174D（C→A；丙氨酸174→天冬氨酸）在来自意大利、瑞士和南斯拉夫的受试者中发现（总频率16%），但在来自英国、法国或美国的受试者中未发现。L288ΔC携带一个单碱基对缺失，导致密码子288处移码，且仅限于西西里岛受试者。通过使用一组有限的等位基因特异性寡核苷酸检测扩增DNA中的这些突变，超过95%的HFI患者将易于进行基因诊断。