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目的通过检测3个Fabry病家系基因突变类型明确基因诊断,并进行家系成员的基因型检测。方法通过PCR和直接测序的方法,对3个Fabry家系的先证者及部分家系成员外周血DNA进行α-半乳糖苷酶A编码GLA基因7个外显子及其相邻内含子的DNA序列检测。结果(1)先证者1的GLA基因7号外显子内1142位点发生碱基缺失(1142delG),1142位碱基G的缺失导致蛋白质翻译在390位氨基酸提前终止,该突变国内外均未见报道;(2)先证者2的GLA基因6号外显子内902位点存在1个错义突变,碱基G被A取代,导致其编码的第301位氨基酸由精氨酸变为谷氨酰胺(902G>A,R301Q);(3)先证者3的GLA基因3号外显子内484位点存在1个错义突变,碱基T被C取代,导致其编码的第142位氨基酸由半胱氨酸变为精氨酸(484T>C,C142R)。在3个家系的部分成员中进行基因检测,检出GLA突变基因携带者共6例,其中男性半合子1例,女性杂合子5例,突变类型均与相应先证者符合。100条正常X染色体对照中均未发现上述位点异常。结论本研究在3个Fabry病家系中检出3种GLA基因突变,其中1142delG为新发现的突变,并在3个家系的部分家系成员中检出男性半合子1例,女性杂合子5例。
OBJECTIVE: To confirm the gene diagnosis by detecting the genotypes of three Fabry’s disease pedigrees and to test the genotypes of pedigree members. Methods PCR and direct sequencing methods were used to detect the DNA sequence of the exon 7 of GLA gene and its adjacent intron in α-galactosidase A from probands and some pedigree members of three Fabry pedigrees. Sequence detection. Results (1) The deletion of 1142delG at 1142 in exon 7 of GLA gene in proband 1 resulted in the early termination of protein translation at the amino acid position 390, which was not found at home or abroad (2) There is a missense mutation at position 902 in exon 6 of GLA gene of proband 2, and base G is replaced by A, resulting in its encoding of the amino acid at position 301 from arginine to valley (902G> A, R301Q). (3) There was a missense mutation at position 484 in exon 3 of GLA gene of proband 3, and the base T was replaced by C, resulting in the encoded amino acid at position 142 From cysteine to arginine (484T> C, C142R). Genes were detected in some members of three families, and 6 carriers of GLA mutation gene were detected, including 1 male hemizygous and 5 female heterozygous. The types of mutations were consistent with the corresponding probands. 100 normal X chromosome control were not found in the above site anomalies. Conclusions In this study, three GLA gene mutations were detected in three Fabry family lines, of which 1142delG was a newly discovered mutation. One male and one female heterozygote were detected in some pedigrees of three pedigrees.