葡萄牙苯丙氨酸羟化酶缺乏所致高苯丙氨酸血症的群体遗传学

Population genetics of hyperphenylalaninaemia resulting from phenylalanine hydroxylase deficiency in Portugal.

作者信息

Rivera I, Leandro P, Lichter-Konecki U, Tavares de Almeida I, Lechner M C

机构信息

Centro de Patogénese Molecular, Faculdade de Farmácia da UL, Lisboa, Portugal.

出版信息

J Med Genet. 1998 Apr;35(4):301-4. doi: 10.1136/jmg.35.4.301.

DOI:10.1136/jmg.35.4.301

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1051278/

Abstract

In order to elucidate the molecular basis of phenylketonuria (PKU) in Portugal, a detailed study of the Portuguese mutant phenylalanine hydroxylase (PAH) genes was performed. A total of 222 mutant alleles from 111 PKU families were analysed for 26 mutations and restriction fragment length polymorphismlvariable number tandem repeat (RFLP/VNTR) haplotypes. It was possible to characterise 55% of the mutant alleles, in which 14 different mutations (R261Q, V388M, IVS10nt-11, I65T, P281L, R252W, R158Q, L348V, Y414C, L311P, Y198fsdel22bp, R408W, R270K, and R261X) and three polymorphisms (Q232Q, V245V, and L385L) were identified. A total of 14 different haplotypes were observed, with a high prevalence of haplotype 1 among mutant and normal alleles. The results reported in this study show considerable genetic heterogeneity in the Portuguese PKU population, as has also been described for other southern European populations.

摘要

为了阐明葡萄牙苯丙酮尿症（PKU）的分子基础，对葡萄牙突变型苯丙氨酸羟化酶（PAH）基因进行了详细研究。对来自111个PKU家庭的222个突变等位基因进行了26种突变以及限制性片段长度多态性/可变数目串联重复序列（RFLP/VNTR）单倍型分析。可以对55%的突变等位基因进行分型，其中鉴定出14种不同的突变（R261Q、V388M、IVS10nt-11、I65T、P281L、R252W、R158Q、L348V、Y414C、L311P、Y198fsdel22bp、R408W、R270K和R261X）以及三种多态性（Q232Q、V245V和L385L）。共观察到14种不同的单倍型，单倍型1在突变等位基因和正常等位基因中均具有较高的发生率。本研究报道的结果表明，葡萄牙PKU人群中存在相当大的遗传异质性，其他南欧人群也有类似情况。

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