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目的分析一个Fabry病家系先证者的临床表现,并进行该家系成员α-半乳糖苷酶A(GLA)基因突变检测。方法回顾性分析该家系先证者临床及病理资料,采用聚合酶链式反应(PCR)直接测序法检测先证者及家系成员GLA基因编码序列。结果①先证者表现为下肢皮肤色素沉着、神经性疼痛和肾脏损害,其弟死于尿毒症。肾活检提示继发性局灶节段性肾小球硬化,肾小球足细胞泡沫变性,电镜发现足细胞内大量同心圆排列的具有层状结构的包涵体,确诊Fabry病。②GLA基因测序检测发现1个无义突变,位于第2号外显子CAG119TAG(Q119T),终止密码提前出现致使形成一条截短的多肽链。家系发现2例杂合子,分别为先证者母亲及侄女。结论本研究从生化、病理及基因水平3个层面诊断了一个Fabry病家系,确诊致病原因为GLA基因点突变〔第2号外显子CAG119TAG(Q119T)〕,该突变在中国人群中首次报道。
Objective To analyze the clinical manifestations of proband in a Fabry family and to detect the mutation of a-galactosidase A (GLA) gene in this family. Methods The clinical and pathological data of probands in this pedigree were retrospectively analyzed. The coding sequence of GLA gene in proband and pedigree was detected by polymerase chain reaction (PCR) direct sequencing. Results ① probands showed lower extremity skin pigmentation, neuropathic pain and kidney damage, his brother died of uremia. Renal biopsy prompted secondary focal segmental glomerulosclerosis, glomerular podocyte degeneration, electron microscopy found a large number of parenchyma cells arranged in a concentric arrangement of laminar inclusions, the diagnosis of Fabry disease. (2) One nonsense mutation was found in the GLA gene sequencing, located on the exon 2 of CAG119TAG (Q119T). The stop codon appeared ahead of time to form a truncated polypeptide chain. Family found 2 cases of heterozygotes, respectively, the proband’s mother and niece. Conclusions In this study, one Fabry family was diagnosed at three levels of biochemistry, pathology and gene level. The cause of the diagnosis was point mutation of GLA (exon 2 CAG119TAG (Q119T)), which was first reported in Chinese population.