Maezawa Yoshiro, Kato Hisaya, Takemoto Minoru, Watanabe Aki, Koshizaka Masaya, Ishikawa Takahiro, Sargolzaeiaval Forough, Kuzuya Masafumi, Wakabayashi Hiroshi, Kusaka Takashi, Yokote Koutaro, Oshima Junko
Department of Clinical Cell Biology and Medicine, Graduate School of Medicine, Chiba University, Chiba.
Department of Medicine, International University of Health and Welfare, Narita.
Mol Syndromol. 2018 Jul;9(4):214-218. doi: 10.1159/000489055. Epub 2018 May 15.
Werner syndrome (WS) is a rare autosomal recessive disorder characterized by systemic accelerated aging. It is caused by pathogenic variants of the gene that encodes a nuclear helicase. In this report, we describe 4 newly identified WS cases among those referred to the Japanese Werner Consortium, Chiba University, Japan. All 4 cases were compound heterozygotes of the Japanese founder mutation, c.3139-1G>C, and a novel null pathogenic variant, c.1587G>A, c.2448+1G>A, or c.3233+1G>T, or an amino acid substitution variant, c.1720G>A, p.Gly574Arg. These 3 null pathogenic variants were not previously described. The p. Gly574Arg was previously reported in a European patient, and the identification of the second p. Gly574Arg case, with classical WS features, further confirmed the pathogenic nature of this variant. For the case with c.3233+1G>T, we determined the phase of 2 disease-causing mutations and demonstrated that they are on different chromosomes. This assay would be particularly important for those cases with ambiguous clinical diagnosis.
沃纳综合征（WS）是一种罕见的常染色体隐性疾病，其特征为全身性加速衰老。它由编码一种核解旋酶的基因突变所致。在本报告中，我们描述了日本千叶大学沃纳综合征研究联盟所收治的4例新确诊的WS病例。所有4例均为日本始祖突变c.3139-1G>C与一种新的无义致病变异（c.1587G>A、c.2448+1G>A或c.3233+1G>T）或一种氨基酸替代变异（c.1720G>A，p.Gly574Arg）的复合杂合子。这3种无义致病变异此前未曾有过描述。p.Gly574Arg此前曾在一名欧洲患者中报道过，而此次发现第二例具有典型WS特征的p.Gly574Arg病例，进一步证实了该变异的致病性。对于携带c.3233+1G>T的病例，我们确定了两个致病突变的相位，并证明它们位于不同的染色体上。该检测方法对于临床诊断不明确的病例尤为重要。
