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GENATLAS PHENOTYPE

last update : 04-09-2019

Symbol	WRN
Location	8p12
Name	Werner syndrome
Corresponding gene	WRN
related resource	Werner Syndrome mutation database
Main clinical features	adult onset segmental progeroid syndrome, characterized by premature ageing, presenile subcapsular posterior cataract (PMID: 27492502)) associated with an increased risk of cancer, a chromosome instability, transient ischaemic attacks secondary to atherosclerosis in the common carotid arteries, sensory peripheral neuropathy and insulin resistance (impaired phosphatidylinositol 3 kinase responsible of malinsertion of SLC2A1 into the plasma membrane) on MRSI significantly lower values of normalized total brain volume and MT ratio in the white matter than age-matched normal controls
Genetic determination	autosomal recessive
Function/system disorder	connective tissue
	eye
Type	disease

Gene product

Name	DNA helicase (WRN)

Mechanism(s)

Gene mutation	Chromosome rearrangement	Effect	Comments
various types		truncated protein	mostly truncated mutations, potentialy leading to shortening telomeres, defective DNA repair in rapidly proliferating cells during DNA replication, acceleration of normal telomere-driven replication senescence, or defect in postreplicational genomic maintenance
	other		increased chromosomal instability

Remark(s)

. genome instability in Werner cells depends directly on telomere dysfunction, linking chromosome end maintenance to chromosomal aberrations NEMO (IKBKG) shuttle may link genotoxic stress to the activation of innate immunity system and cause premature aging via inflamm-aging process