Werner syndrome is an autosomal recessive disorder characterized by premature aging and genomic instability. Clinical manifestations of Werner syndrome include loss and graying of hair, hoarseness, and scleroderma-like skin changes starting in the 20s, followed by bilateral ocular cataracts, type 2 diabetes mellitus, hypogonadism, skin ulcers, and osteoporosis in the 30s. A characteristic facial appearance termed "bird-like" due to the pinched look at the bridge of the nose evolves in the third or fourth decade. Affected individuals exhibit several forms of arteriosclerosis, the most serious form of which is coronary atherosclerosis that may lead to myocardial infarction which, together with cancer, is the most common cause of death, typically about age 48 years.
Bartal et al. (1996) described a 51-year-old Bedouin male with Werner's syndrome, diagnosed as erythroleukemia (AML-6), and presenting as acute pancytopenia. The patient died two months after diagnosis. This was a rare case of erythroleukemia in a patient with Werner's syndrome.
In 3 sibs with Werner syndrome in a Syrian family, Yu et al. (1996) found a 4-bp deletion spanning a splice junction in the WRN gene in homozygous state. The mutation causes a frameshift and premature stop codon at residue 1393. A fourth sib, aged 21 years, was homozygous for the same mutation but was too young for a definitive diagnosis of Werner syndrome. Although these individuals were not from a consanguineous marriage, they did share the same haplotype across the WRN region. Oshima et al. (1996) analyzed the DNA of male patient from the Syrian family reported by Yu et al. (1996). By applying an RT-PCR protocol, they demonstrated the presence of a deletion of 4 bp, ACAG, from the beginning of exon 2. The ACAG deletion would result in a termination at nt 3971-3973 TAG (Stp).