Werner Syndrome in a Korean Man

A 34-year-old Korean man living in Tokyo was referred to us in January 1999 for control of his diabetes during cataract surgery. He told us that both disorders had first appeared when he was 22, along with hyperlipidemia. He had acute pancreatitis at 24, and acute appendicitis with peritonitis at 27. He was admitted to a hospital in 1998 for ileus. He has three siblings, the youngest of whom, a sister, had cataracts at 22, and her hair was streaked with gray. His father was diabetic and died at 52 from liver cancer. His mother has angina pectoris—she is 58. His father was from Masan and his mother from Pusan, both cities in southern Korea. They were not related and no relatives were known to have a medical disorder similar to that of our patient. Inclusion of Japanese ancestry was denied at least over several generations.

A physical examination showed that our patient’s height was 162.8 cm, and body weight was 54.8 kg. His hair was gray and he had sclerotic skin, a high-pitched voice, and bilateral cataracts. He said he had erectile dysfunction.

His fasting plasma glucose level was 5.4 mmol/l and HbA_1c level was 6.2%. Total cholesterol level was 7.24 mmol/l and triglyceride level was 12.0 mmol/l. Liver chemistry and abdominal echogram showed a fatty liver. Gastrointestinal endoscopy was done because of epigastric pain, indicating a superficial gastritis. Electrocardiogram with double Master load revealed a normal exercise tolerance. He was suspected of having Werner syndrome based on his premature aging phenotypes and his family history.

Gene analysis was done after obtaining informed consent, but the three major mutations (mutations 1, 4, and 6), which account for ∼90% of Japanese patients with Werner syndrome, were not detected (1). However, Western blot analysis using the patient’s transformed lymphocytes revealed a defect in the production of WRN RecQ helicase, the WRN gene product (2). This indicated the possibility of the truncated protein derived from the mutated WRN gene.

Of the cases of Werner syndrome worldwide, 75% are found in Japanese patients (3). Interestingly, there have been no Koreans reported in the Japanese registry, which is a list of ∼1,000 patients with Werner syndrome, in spite of the racial and geographical adjacency to Japan. The rarity of Werner syndrome in Korean individuals might be partially explained by the small amount of consanguineous marriages influenced by traditional Confucianism. Also, the major WRN gene mutations found in Japanese patients may have arisen after they separated from their common ancestry with Koreans. This Korean patient may be a solitary case.

However, the genetic difference in this case from those reported and studied in Japan contributes to the understanding of the disease, as such differences have in studies of the syndrome’s subtypes in Caucasians.