Definitive diagnosis of mandibular hypoplasia, deafness, progeroid features and lipodystrophy (MDPL) syndrome caused by a recurrent de novo mutation in the POLD1 gene
Definitive diagnosis of mandibular hypoplasia, deafness, progeroid features and lipodystrophy (MDPL) syndrome caused by a recurrent de novo mutation in the POLD1 gene
复制标题
DOI：
10.1507/endocrj.ej17-0287
复制
发表时间：
2018-01-01
影响因子：
2
通讯作者：
Kaname, Tadashi
中科院分区：
文献类型：
--
作者：
Sasaki, Haruka;Yanagi, Kumiko;Kaname, Tadashi
节段性早老综合征伴脂肪营养不良是一种极其罕见、异质性和复杂的多系统疾病，其特征在于影响各种组织和器官的过早衰老的表型特征。在这项研究中，我们提出了一个“散发/孤立”的日本妇女谁最终被诊断为下颌骨发育不全，耳聋，早衰症的特点，进行性脂肪营养不良（MDPL）综合征（MIM #615381）使用全外显子测序分析。根据30年的观察结果，怀疑她患有非典型沃纳综合征和/或早衰综合征;然而，通过桑格测序进行的重复基因检测未发现与先天性部分脂肪营养不良（CPLD）和/或下颌骨发育不良伴脂肪营养不良（MAD）的各种亚型相关的任何致病突变。最近，MDPL综合征已被描述为一个新的实体表现为进行性脂肪营养不良。此外，已在MDPL综合征患者中确定了19号染色体上的聚合酶δ 1（POLD 1）基因突变。迄今为止，全球已报告了21例POLD 1相关MDPL综合征病例，尽管几乎全部来自欧洲。在这里，我们确定了一个从头突变外显子15（p.Ser605del）的POLD 1基因在日本的情况下，通过全外显子组测序。据我们所知，这是日本首例确诊的MDPL综合征病例。我们的研究结果提供了进一步的证据，POLD 1突变是MDPL综合征的原因，并在不同种族中作为一个共同的遗传决定因素。
Segmental progeroid syndromes with lipodystrophy are extremely rare, heterogeneous, and complex multi-system disorders that are characterized by phenotypic features of premature aging affecting various tissues and organs. In this study, we present a "sporadic/isolated" Japanese woman who was ultimately diagnosed with mandibular hypoplasia, deafness, progeroid features, and progressive lipodystrophy (MDPL) syndrome (MIM #615381) using whole exome sequencing analysis. She had been suspected as having atypical Werner syndrome and/or progeroid syndrome based on observations spanning a 30-year period; however, repeated genetic testing by Sanger sequencing did not identify any causative mutation related to various subtypes of congenital partial lipodystrophy (CPLD) and/or mandibular dysplasia with lipodystrophy (MAD). Recently, MDPL syndrome has been described as a new entity showing progressive lipodystrophy. Furthermore, polymerase delta 1 (POLD1) gene mutations on chromosome 19 have been identified in patients with MDPL, syndrome. To date, 21 cases with POLD1-related MDPL syndrome have been reported worldwide, albeit almost entirely of European origin. Here, we identified a de novo mutation in exon 15 (p.Ser605del) of the POLD1 gene in a Japanese case by whole exome sequencing. To the best of our knowledge, this is the first identified case of MDPL syndrome in Japan. Our results provide further evidence that mutations in POLD1 are responsible for MDPL syndrome and serve as a common genetic determinant across different ethnicities.