【摘要】 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。② GLA基因测序检测发现1个无义突变，位于第2号外显子CAG119AG（Q119），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CAG119AG(Q119)〕，该突变在中国人群中首次报道。
英文摘要:
【Abstract】 Objective To analyze the clinical manifestation, clinicopathologic features and alpha-galactosidase A (GLA) gene mutations in a pedigree with Fabry disease. Methods In this study, we retrospectively collected the clinical data of the members in the pedigree with Fabry disease, then the clinicopathologic features of the male proband were analyzed by renal biopsy, and GLA gene was detected by PCR and direct sequencing. Results ①The proband was characterized by pigmentation of bilateral lower extremities, episodes of neuropathic pain, and renal dysfunction. The renal biopsy showed secondary focal segmental glomerulosclerosis with massive foam-cell liked podocytes under light microscope and abundant inclusions in podocytes which were round，comprising concentric layers of dense material separated by clear spaces under electron microscope.②The proband was identified to present a missense mutation as CAG119TAG (Q119T). The mother and niece of the proband were the carriers of this missense mutation. Conclusion We identified a family with Fabry disease resulting from a novel point mutation of GLA gene, which has not been reported before in Chinese population.
