Identification of a novel mutation in the polymerase delta 1 (POLD1) gene in a lipodystrophic patient affected by mandibular hypoplasia, deafness, progeroid features (MDPL) syndrome
Identification of a novel mutation in the polymerase delta 1 (POLD1) gene in a lipodystrophic patient affected by mandibular hypoplasia, deafness, progeroid features (MDPL) syndrome
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DOI：
10.1016/j.metabol.2014.07.010
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发表时间：
2014-11-01
影响因子：
9.8
通讯作者：
Santini, Ferruccio
中科院分区：
文献类型：
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作者：
Pelosini, Caterina;Martinelli, Silvia;Santini, Ferruccio
Objective.进行性脂肪营养不良是罕见的MDPL综合征的主要特征之一。到目前为止，已描述了9例受此综合征影响的患者，最近的一项研究在其中4例中发现了POLD 1基因中单个密码子的框内缺失（Ser 605 del）。POLD 1基因在不同位点的序列改变以前已在人类结直肠癌和子宫内膜癌中报道。一位48岁的女性因先前诊断为脂肪代谢障碍而被收住我科进行评估。她没有报告糖尿病或其他代谢紊乱的家族史。她25岁时偶然被诊断出高血压。当时，她还被诊断出患有感觉神经性双侧听力损失。在体格检查时，她表现出几乎影响整个身体的脂肪萎缩、下颌发育不全、鸟样脸、喙鼻、早老样面部特征、牙齿拥挤、小口和悬雍垂。腹部超声显示肝肿大和肝脂肪变性。DXA测量的脂肪质量指数为4.59 kg/m2，表明脂肪不足;口服葡萄糖耐量试验显示葡萄糖耐量受损。对POLD 1基因编码区进行全序列分析，发现一个新的杂合突变（R507 C）。本文描述的MDPL患者在POLD 1的核酸外切酶结构域中具有新突变。这种新的变异为POLD 1在MDPL发病机制中的作用提供了进一步的证据。将蛋白质不同位点的变化与不同疾病联系起来的机制仍有待澄清。(C)2014 Elsevier Inc. All rights reserved.
Objective. Progressive lipodystrophy is one of the major features of the rare MDPL syndrome. Until now, 9 patients affected by this syndrome have been described and a recent study identified in 4 of them an in-frame deletion (Ser605del) of a single codon in the POLD1 gene. Sequence alterations of the POLD1 gene at different sites have been previously reported in human colorectal and endometrial carcinomas.Materials/methods. A 48-year-old woman was admitted to our department for the assessment of a previously diagnosed lipodystrophy. She did not report a family history of diabetes or other metabolic disorders. Hypertriglyceridemia was diagnosed incidentally when she was 25 years old. At that time she was also diagnosed with sensorineural bilateral hearing loss. At physical examination she presented lipoatrophy affecting nearly the entire body, mandibular hypoplasia, bird-like face, beaked nose, progeroid facial features, with crowded teeth, small mouth and uvula. Abdominal ultrasound showed hepatomegaly and hepatosteatosis. Fat mass index measured with DXA was 4.59 kg/m(2), indicating a fat deficit; the oral glucose tolerance test showed an impaired glucose tolerance.Results. Sequence analysis of the entire coding region of the POLD1 gene, disclosed a novel heterozygous mutation in exon 13 (R507C).Conclusion. The MDPL patient herein described harbors a novel mutation in the exonuclease domain of POLD1. This new variant provides further evidence for a role of POLD1 in the pathogenesis of MDPL. The mechanisms that link changes at various sites of the protein with different diseases remain to be clarified. (C) 2014 Elsevier Inc. All rights reserved.