Werner syndrome and mutations of the WRN and LMNA genes in France.
Werner syndrome (WS) is a pleiotropic disease of premature aging involving short stature, tight, atrophied, and/or ulcerated skin; a characteristic 'birdlike' facies and high, squeaky or hoarse voice; premature greying and thinning of the hair; and early onset cataracts. Additional common symptoms include diabetes mellitus, hypogonadism, osteoporosis, osteosclerosis of the digits, soft tissue calcification, premature atherosclerosis, rare or multiple neoplasms, malformed teeth, and flat feet. Diagnosis can be difficult due to the variable presentation and rarity of the disorder. Transmission is usually autosomal recessive. The WS gene, WRN, is member of the RecQ DNA helicase family. Biallelic mutations of WRN are responsible for most patients. Although heterozygous missense mutations in the LMNA gene have been observed in severely affected WS patients, this only accounts for a small fraction of non-WRN patients. Eighteen WS cases were referred to us for molecular analysis. Eleven had definite and three had probable WS according to the University of Washington Registry clinical criteria. All exons of the WRN gene and their splice junctions were sequenced. Of the fourteen definite or probable cases, 11 had one or more WRN mutation. Thirteen different mutations were found, and ten of these were previously undescribed. There were few phenotypic differences between patients with WRN mutation(s) and those who met clinical criteria though lacking WRN mutations. However, patients with mutations tended to have more symptoms overall, and mutations were not observed in the two cases with cardiomyopathy.
Uhrhammer
Nancy A
NA
Laboratoire Diagnostic Génétique et Moléculaire, Centre Jean Perrin, Clermont-Ferrand, France. nancy.uhrhammer@cjp.fr
Lafarge
Laurence
L
Dos Santos
Laetitia
L
Domaszewska
Anna
A
Lange
Magdalena
M
Yang
Yong
Y
Aractingi
Selim
S
Bessis
Didier
D
Bignon
Yves-Jean
YJ
D000328:Adult; D002648:Child; D004265:DNA Helicases / Q000235:genetics*; D004252:DNA Mutational Analysis; D005090:Exodeoxyribonucleases; D005260:Female; D018703:Founder Effect; D005602:France / Q000453:epidemiology; D006801:Humans; D034904:Lamin Type A / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011110:Polymorphism, Genetic; D053484:RecQ Helicases; D014898:Werner Syndrome / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics; D000071657:Werner Syndrome Helicase
C494847:LMNA protein, human; D034904:Lamin Type A; D005090:Exodeoxyribonucleases; D004265:DNA Helicases; D053484:RecQ Helicases; C098785:WRN protein, human; D000071657:Werner Syndrome Helicase