A Novel Mutation in a Patient with Werner’s Syndrome

<i>Background:</i> Werner’s syndrome, a rare autosomal recessive disorder, is characterized by features of premature aging. Seventy-five percent of the alleles of Japanese patients with Werner’s syndrome have one of three major mutations. <i>Objective:</i> To determine the genotype of a patient with Werner’s syndrome. <i>Methods:</i> We diagnosed Werner’s syndrome in a 47-year-old Japanese man who had juvenile cataracts, skin sclerosis and hyperpigmentation of the feet, a high-pitched voice, characteristic bird-like appearance of the face with a beak-shaped nose, thinning of the skin over the whole body and hyperkeratoses on the soles of the feet, hyperlipidemia, and diabetes mellitus. None of his immediate family had entered into a consanguineous marriage. He had undergone surgery to treat duodenal perforation. We screened his family for three major mutations (mutations 1, 4, 6) in the WRN gene by polymerase chain reaction-restriction fragment length polymorphism. Automated DNA sequencing fluorescence-labeled dideoxy terminators proceeded for abnormally migrating bands. <i>Results:</i> The patient and his mother had mutation 1 (nonsense mutation) in one chromosome. Although mutations 4 and 6 were undetectable, screening for mutation 4 revealed an abnormally migrating band. Consequently, we discovered a novel 4-bp deletion in exon 25 only in the patient. This mutation was not detected in any other family member. <i>Conclusion:</i> This is the first description of a patient with Werner’s syndrome who has a compound heterozygote of mutation 1 and a novel deletion mutation.