Werner Syndrome

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This Wiki Page was created and it is maintained by Mainá Bitar for the "Protein Structure and Function Analysis Practical" of 2011 (SS).

INTRODUCTION

The Werner Syndrome (WS) is an autosomal recessive disorder, also known as Adult Progeria. The syndrome was described for the first time in 1904 by Otto Werner (and therefore, named after him), in his PhD thesis entitled “Über katarakt in Verbindung mit Sklerodermie” (which can be translated to “About cataracts connected to sclerodermia”). In the first 90 years of research concerning WS, over 1000 patients were reported, 75% of which were Japanese descent (figure 1) [1]. WS is one of the several types of segmental progeroid syndromes, which affect multiple tissues and organs (on the other hand, unimodal syndromes predominantly affect a single organ) [2]. As one can expect, the most notable symptoms of WS mimic the background of the most general condition called Progeria, with a complex phenotype of accelerated aging. The patients prematurely acquire the appearance of someone several decades older, accompanied by loss or graying of hair, scleroderma-like skin and voice alterations, usually around the second or third decade of life [3]. The phenotype of WS was previously summarized as a “caricature of aging” [1].

In general, the subjects develop normally until adolescence, when there is absence of the common growth spurt. The clinical manifestations usually include atherosclerosis, osteoporosis, diabetes, lenticular cataracts, heart failure, cancer and other age-related conditions that appear during early adulthood, following puberty (figure 2) [1, 2]. The typical cause of death is cancer or cardiovascular disease, often occurring between the fourth and fifth decades of life. While in 1966, the median age of death was 47 years [4], in 1997, Makoto Goto reported a surprising median age of death of 54 years [2]. At the cellular level, a reduction in the replicative rate is often observed (cellular senescence) and genomic instability is present in the form of chromosome breaks and translocations, as well as large deletions at the molecular level. A higher occurrence of somatic mutations is also related to the syndrome [1-4].