WRN Mutation Update: Mutation Spectrum, Patient Registries, and Translational Prospects.
Werner syndrome (WS) is a rare autosomal recessive disorder characterized by a constellation of adult onset phenotypes consistent with an acceleration of intrinsic biological aging. It is caused by pathogenic variants in the WRN gene, which encodes a multifunctional nuclear protein with exonuclease and helicase activities. WRN protein is thought to be involved in optimization of various aspects of DNA metabolism, including DNA repair, recombination, replication, and transcription. In this update, we summarize a total of 83 different WRN mutations, including eight previously unpublished mutations identified by the International Registry of Werner Syndrome (Seattle, WA) and the Japanese Werner Consortium (Chiba, Japan), as well as 75 mutations already reported in the literature. The Seattle International Registry recruits patients from all over the world to investigate genetic causes of a wide variety of progeroid syndromes in order to contribute to the knowledge of basic mechanisms of human aging. Given the unusually high prevalence of WS patients and heterozygous carriers in Japan, the major goal of the Japanese Consortium is to develop effective therapies and to establish management guidelines for WS patients in Japan and elsewhere. This review will also discuss potential translational approaches to this disorder, including those currently under investigation.
Department of Clinical Cell Biology and Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan.
Koutaro
K
Yokote
Department of Medicine, Division of Medical Genetics, University of Washington, Seattle, Washington.
Sirisak
S
Chanprasert
Department of Pathology, University of Washington, Seattle, Washington.
Lin
L
Lee
Department of Human Genetics, University of Wuerzburg, Wuerzburg, Germany.
Katharina
K
Eirich
Department of Clinical Cell Biology and Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan.
Minoru
M
Takemoto
Department of Clinical Cell Biology and Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan.
Aki
A
Watanabe
Department of Clinical Cell Biology and Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan.
Naoko
N
Koizumi
Institute of Human Genetics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Davor
D
Lessel
Department of Pediatrics, Division of Genetic Medicine, University of Washington, Seattle, Washington.
Takayasu
T
Mori
Department of Medicine, Division of Medical Genetics, University of Washington, Seattle, Washington.
Fuki M
FM
Hisama
Department of Pathology, University of Washington, Seattle, Washington.
Paula D
PD
Ladd
Advocate Lutheran General Hospital and Advocate Children's Hospital, Park Ridge, Illinois.
Brad
B
Angle
The Genetics Institute, Rambam Health Care Campus and Rappaport School of Medicine, Technion - Israel Institute of Technology, Haifa, Israel.
Hagit
H
Baris
Department of Internal Medicine, Division of Medical Genetics, Istanbul Medical Faculty, Istanbul University, Turkey.
Kivanc
K
Cefle
Department of Internal Medicine, Division of Medical Genetics, Istanbul Medical Faculty, Istanbul University, Turkey.
Sukru
S
Palanduz
Department of Internal Medicine, Division of Medical Genetics, Istanbul Medical Faculty, Istanbul University, Turkey.
Sukru
S
Ozturk
Department of Dermatology, Greys Hospital, Pietermaritzburg, South Africa.
Antoinette
A
Chateau
Department of Neurology, Okayama City Hospital, Okayama, Japan.
Kentaro
K
Deguchi
Milestone Hospital, Rajkot, India.
T K M
TK
Easwar
Department of Medicine, Surgery and Neurosciences, Unit Clinical Neurology and Neurometabolic Diseases, Medical School, University of Siena, Siena, Italy.
Antonio
A
Federico
Department of Dermatology, University of North Carolina, Chapel Hill, North Carolina.
Amy
A
Fox
Division of Genetics and Metabolism, Phoenix Children's Hospital, Phoenix, Arizona.
Theresa A
TA
Grebe
Division of Genetics, UMass Memorial Medical Center, Worcester, Massachusetts.
Beverly
B
Hay
Department of Pediatric Genetics, Amrita Institute of Medical Sciences and Research Center, Kochi, Kerala, India.
Sheela
S
Nampoothiri
Department of Medicine, New York Medical College, Hawthorne, New York.
Karen
K
Seiter
Division of Genetics, University of Maryland School of Medicine, Baltimore, Maryland.
Elizabeth
E
Streeten
Centro Médico Nacional 20 de Noviembre, ISSSTE, Mexico City, Mexico.
Raul E
RE
Piña-Aguilar
Genetic Health Service NZ, Wellington, New Zealand.
Gemma
G
Poke
University Medical Center, Utrecht, Netherlands.
Martin
M
Poot
Department of Clinical Genetics, Podlaskie Medical Center, Bialystok, Poland.|Department of Perinatology, Medical University of Bialystok, Bialystok, Poland.
Renata
R
Posmyk
Department of Pathology, University of Washington, Seattle, Washington.
George M
GM
Martin
Institute of Human Genetics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Christian
C
Kubisch
Department of Human Genetics, University of Wuerzburg, Wuerzburg, Germany.
Detlev
D
Schindler
Department of Clinical Cell Biology and Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan.|Department of Pathology, University of Washington, Seattle, Washington.
Junko
J
Oshima
D000367:Age Factors; D000818:Animals; D030541:Databases, Genetic; D004195:Disease Models, Animal; D005091:Exons; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005843:Geography; D006801:Humans; D007564:Japan; D051379:Mice; D009154:Mutation; D010641:Phenotype; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D012042:Registries; D057170:Translational Research, Biomedical; D064878:Web Browser; D014898:Werner Syndrome / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D000071657:Werner Syndrome Helicase / Q000235:genetics*
C098785:WRN protein, human; D000071657:Werner Syndrome Helicase
Progeroid syndrome; RECQ3; RECQL2; RecQ helicase; WRN; Werner syndrome
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