This report describes Werner syndrome (WRN), a premature aging syndrome associated with aged appearance and early development of age-related diseases; symptoms begin to appear post-puberty. Werner syndrome exhibits autosomal recessive inheritance. The human gene implicated in this disease is Werner syndrome RecQ-like helicase (WRN or RECQL2), which is is thought to be involved in the repair of double-strand DNA breaks. There is a single ortholog in Drosophila, WRNexo, which shares a similar exonuclease domain, but lacks the helicase domain found in the human gene. Classical amorphic and hypomorphic alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated for Dmel\WRNexo.
The human WRN gene has not been introduced into flies. Several of the mutational lesions implicated in Werner syndrome are within the exonuclease domain of the human WRN gene.
Animals homozygous for an amorphic allele of Dmel\WRNexo have significantly reduced hatching frequency; embryos have more nuclear division defects (increased number of anaphase bridges and gaps between nuclei) and significantly increased double-strand breaks compared to wild type. A single genetic interaction has been described for WRNexo; see the WRNexo gene report.
[updated Sep. 2017 by FlyBase; FBrf0222196]
[WERNER SYNDROME; WRN](https://omim.org/entry/277700)
[RECQ PROTEIN-LIKE 2; RECQL2](https://omim.org/entry/604611)
Werner syndrome is characterized by the dramatic, rapid appearance of features associated with normal aging. Individuals with this disorder typically grow and develop normally until they reach puberty. Affected teenagers usually do not have a growth spurt, resulting in short stature. The characteristic aged appearance of individuals with Werner syndrome typically begins to develop when they are in their twenties and includes graying and loss of hair; a hoarse voice; and thin, hardened skin. They may also have a facial appearance described as "bird-like." Many people with Werner syndrome have thin arms and legs and a thick trunk due to abnormal fat deposition. As Werner syndrome progresses, affected individuals may develop disorders of aging early in life. People with Werner syndrome usually live into their late forties or early fifties. The most common causes of death are cancer and atherosclerosis. (Genetics Home Reference, Werner syndrome; 2017.09.07)
The features of Werner syndrome are scleroderma-like skin changes, especially in the extremities, cataract, subcutaneous calcification, premature arteriosclerosis, diabetes mellitus, a wizened and prematurely aged face, short stature, slender limbs, and stocky trunk. [from MIM:277700; 2017.09.07]
Werner syndrome is caused by homozygous or compound heterozygous mutation in the RECQL2 gene. [from MIM:277700; 2017.09.07]
Somatic cells from Werner syndrome patients reveal a propensity to develop chromosomal aberrations, including translocations, inversions, and deletions (Salk, 1982; pubmed:6759366). [from MIM:277700; 2017.09.07]
The WRN gene encodes RECQL2, a member of the RecQ subfamily; RECQL2 has both magnesium- and ATP-dependent DNA-helicase activity and 3' to 5' exonuclease activity towards double-stranded DNA; it is thought to be involved in the repair of double-strand DNA breaks. [Gene Cards, WRN; 2017.09.07]
The human WRN gene encodes a larger protein with both an exonuclease domain and a helicase domain; the fly WRNexo gene encodes a smaller protein with only an exonuclease domain. Additional related genes in Drosophila (both exonucleases and helicases) are more closely related to other human genes.
