A cascade leading to premature aging phenotypes including abnormal tumor profiles in Werner syndrome (review).

[werner syndrome]

This perspective review focused on the Werner syndrome (WS ) by addressing the issue of how a single mutation in a WRN gene encoding WRN DNA helicase induces a wide range of premature aging phenotypes accompanied by an abnormal pattern of tumors . The key event caused by WRN gene mutation is the dysfunction of telomeres . Studies on normal aging have identified a molecular circuit in which the dysfunction of telomeres caused by cellular aging activates the TP 53 gene . The resultant p 53 suppresses cell growth and induces a shorter cellular lifespan , and also compromises mitochondrial biogenesis leading to the overproduction of reactive oxygen species (ROS ) causing multiple aging phenotypes . As an analogy of the mechanism in natural aging , we described a hypothetical mechanism of premature aging in WS : telomere dysfunction induced by WRN mutation causes multiple premature aging phenotypes of WS , including shortened cellular lifespan and inflammation induced by ROS , such as diabetes mellitus . This model also explains the relatively late onset of the disorder , at approximately age 20 . Telomere dysfunction in WS is closely correlated with abnormality in tumorigenesis . Thus , the majority of wide and complex pathological phenotypes of WS may be explained in a unified manner by the cascade beginning with telomere dysfunction initiated by WRN gene mutation .

Diseases
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Diseases presenting "wide range" symptom

22q11.2 deletion syndrome

acute rheumatic fever

adrenomyeloneuropathy

alexander disease

allergic bronchopulmonary aspergillosis

alpha-thalassemia

aromatase deficiency

benign recurrent intrahepatic cholestasis

cadasil

carcinoma of the gallbladder

congenital toxoplasmosis

cowden syndrome

cystinuria

dystrophic epidermolysis bullosa

epidermolysis bullosa simplex

erdheim-chester disease

fabry disease

gm1 gangliosidosis

harlequin ichthyosis

homocystinuria without methylmalonic aciduria

hydrocephalus with stenosis of the aqueduct of sylvius

legionellosis

neonatal adrenoleukodystrophy

oral submucous fibrosis

pendred syndrome

phenylketonuria

pleomorphic liposarcoma

primary effusion lymphoma

primary hyperoxaluria type 1

proteus syndrome

pyruvate dehydrogenase deficiency

scrub typhus

systemic capillary leak syndrome

thoracic outlet syndrome

triple a syndrome

trochlear dysplasia

well-differentiated liposarcoma

werner syndrome

x-linked adrenoleukodystrophy

zellweger syndrome

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