A novel mutation in a patient with Werner's syndrome.
BACKGROUND
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.


OBJECTIVE
To determine the genotype of a patient with Werner's syndrome.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Nakayama
Tomohiro
T
Division of Receptor Biology, Advanced Medical Research Center, Nihon University School of Medicine, Tokyo, Japan. tnakayam@med.nihon-u.ac.jp
Ochiai
Toyoko
T
Takahashi
Yoshiko
Y
Ohkubo
Kimie
K
Hironaga
Takashi
T
Kokubun
Shinichiro
S
D002872:Chromosome Deletion; D004378:Duodenal Diseases / Q000601:surgery; D005838:Genotype; D006801:Humans; D007416:Intestinal Perforation / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012150:Polymorphism, Restriction Fragment Length; D014898:Werner Syndrome / Q000235:genetics*