Focal segmental glomerulosclerosis in patients with mandibuloacral dysplasia owing to ZMPSTE24 deficiency
Focal segmental glomerulosclerosis in patients with mandibuloacral dysplasia owing to ZMPSTE24 deficiency
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DOI：
10.2310/6650.2006.05068
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发表时间：
2006-05-01
影响因子：
2.6
通讯作者：
Garg, Abhimanyu
中科院分区：
文献类型：
--
作者：
Agarwal, Anil K.;Zhou, Xin J.;Garg, Abhimanyu
背景资料：下颌骨肢端发育不良（MAD）是一种罕见的常染色体隐性遗传疾病，其特征是骨骼异常，如下颌骨和锁骨发育不全和肢端骨质溶解。其他特征包括皮肤萎缩和脂肪营养不良。已知有两个遗传基因座可导致MAD：核纤层蛋白A/C（LMNA），编码结构核纤层蛋白，和锌金属蛋白酶（ZMPSTE 24），一种膜结合内切蛋白酶，其参与前核纤层蛋白A的羧基末端残基的翻译后蛋白水解切割以形成成熟核纤层蛋白A。在另一名患有MAD的患者中ZMPSTE 24的突变分析和突变体ZMPSTE 24在酵母生长停滞信息素中的功能活性的测定结果：我们先前报道了一名患有MAD的比利时妇女，她有ZMPSTE 24突变，在27.5岁时死于慢性肾衰竭并发症。我们现在报告一名37岁的澳大利亚男子与MAD谁也有复合杂合突变ZMPSTE 24基因，一个无效突变，Phe 361 fsX 379，和错义突变，Asn 265 Ser，这是部分活跃的酵母互补试验。他还患上了终末期肾病，尽管接受了尸体肾移植，但在37岁时过早死亡。这两个病人的肾活检发现局灶节段性肾小球硬化症，和女性患者的塌陷variant.Conclusion：这些观察表明局灶节段性肾小球硬化症作为ZMPSTE 24缺乏症患者的表型表现。
Background: Mandibuloacral dysplasia (MAD) is a rare autosomal recessive disorder characterized by skeletal abnormalities such as hypoplasia of the mandible and clavicles and acro-osteolysis. Other features include cutaneous atrophy and lipodystrophy. Two genetic loci are known for MAD: lamin A/C (LMNA), encoding structural nuclear lamina proteins, and zinc metalloproteinase (ZMPSTE24), a membrane-bound endoprotease involved in post-translational proteolytic cleavage of carboxy terminal residues of prelamin A to form mature lamin A.Methods: Mutational analysis of ZMPSTE24 in an additional patient with MAD and determination of functional activity of mutant ZMPSTE24 in a yeast growth arrest pheromone diffusion (halo) assay.Results: We previously reported a Belgian woman with MAD who had ZMPSTE24 mutations and died of complications of chronic renal failure at the age of 27.5 years. We now report a 37-year-old Australian man with MAD who also had compound heterozygous mutations in the ZMPSTE24 gene, a null mutation, Phe361fsX379, and a missense mutation, Asn265Ser, which is partially active in the yeast complementation assay. He also developed end-stage renal disease and, despite receiving a cadaveric renal transplantation, died prematurely at the age of 37 years. Renal biopsies of both patients revealed focal segmental glomerulosclerosis, and the female patient had the collapsing variant.Conclusion: These observations suggest focal segmental glomerulosclerosis as a phenotypic manifestation in patients with ZMPSTE24 deficiency.