Neonatal screening for hereditary fructose intolerance: Frequency of the most common mutant aldolase B allele (A149P) in the British population
Neonatal screening for hereditary fructose intolerance: Frequency of the most common mutant aldolase B allele (A149P) in the British population
复制标题
DOI：
10.1136/jmg.33.10.837
复制
发表时间：
1996-10-01
影响因子：
4
通讯作者：
Cox, TM
中科院分区：
文献类型：
--
作者：
James, CL;Rellos, P;Cox, TM
遗传性果糖不耐受(HFI)会导致婴儿和儿童严重的、有时是致命的代谢紊乱，但对饮食治疗有反应。为了确定筛查新生儿HFI的可行性，我们调查了醛缩酶B最常见和最广泛的突变等位基因A149P在新生儿人群中的频率。聚合酶链式反应被用来扩增保存在格思里卡片上的干血标本DNA中的醛缩酶B外显子5的基因组序列。A149P突变通过等位基因特异性寡核苷酸的判别性杂交和限制性内切酶BsaHI的消化独立确认。随机抽取的2050名1994~1995年出生的受试者的血液样本进行醛缩酶B基因的分子分析，鉴定出27个A149P杂合子，1.32+/-0.49%(95%可信水平)。虽然没有鉴定出A149P纯合子，但数据允许预测该等位基因每23000个纯合子中有1个的频率。我们的发现对在英国建立介入性大规模筛查计划以识别患有HFI的新生儿具有一定的意义。
Hereditary fructose intolerance (HFI) causes severe and sometimes fatal metabolic disturbances in infants and children but responds to dietary treatment. To determine the practicability of screening newborn infants for HFI, we have investigated the frequency of the most common and widespread mutant allele of aldolase B, A149P, in the neonatal population. The polymerase chain reaction was used to amplify aldolase B exon 5 genomic sequences in DNA present in dried blood specimens preserved on Guthrie cards. The A149P mutation was identified by discriminatory hybridisation to allele specific oligonucleotides and confirmed independently by digestion with the restriction endonuclease BsaHI, Twenty-seven A149P heterozygotes were identified by the molecular analysis of aldolase B genes in blood samples obtained from a random cohort of 2050 subjects born in 1994 and 1995, 1.32 +/- 0.49% (95% confidence level). Although no A149P homozygotes were identified, the data allow the frequency of 1 in 23 000 homozygotes for this allele to be predicted. Our findings have implications for establishing an interventional mass screening programme to identify newborn infants with HFI in the UK.