IDENTIFICATION OF A POINT MUTATION IN THE HUMAN LYSOSOMAL ALPHA-GLUCOSIDASE GENE CAUSING INFANTILE GLYCOGENOSIS TYPE-II
IDENTIFICATION OF A POINT MUTATION IN THE HUMAN LYSOSOMAL ALPHA-GLUCOSIDASE GENE CAUSING INFANTILE GLYCOGENOSIS TYPE-II
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DOI：
10.1016/0006-291x(91)91906-s
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发表时间：
1991-09-16
影响因子：
3.1
通讯作者：
REUSER, AJJ
中科院分区：
文献类型：
--
作者：
HERMANS, MMP;DEGRAAFF, E;REUSER, AJJ
在一个血缘关系密切的印度家庭中，两名患有婴儿糖原增多症II型的患者被发现在人类溶酶体α-葡萄糖苷酶基因第11外显子上有G到A的转变。两名患者都是纯合子，父母双方都是突变等位基因杂合子。该突变导致了521位氨基酸的Glu到Lys的替换，距离Asp-518的催化位置只有三个氨基酸。该突变被引入野生型溶酶体α-葡萄糖苷酶基因中，并在体外和体内表达。谷氨酸到赖氨酸的取代被证明解释了患者溶酶体α-葡萄糖苷酶前体的异常物理性质，并防止了催化活性酶的形成。在纯合子形式中，它会导致严重的婴儿糖原增多症II型表型。
Two patients in a consanguineous Indian family with infantile glycogenosis type II were found to have a G to A transition in exon 11 of the human lysosomal α-glucosidase gene. Both patients were homozygous and both parents were heterozygous for the mutant allele. The mutation causes a Glu to Lys substitution at amino acid position 521, just three amino acids downstream from the catalytic site at Asp-518. The mutation was introduced in wild type lysosomal α-glucosidase cDNA and the mutant construct was expressedin vitroandin vivo. The Glu to Lys substitution is proven to account for the abnormal physical properties of the patients lysosomal α-glucosidase precursor and to prevent the formation of catalytically active enzyme. In homozygous form it leads to the severe infantile phenotype of glycogenosis type II.