Biallelic WRN Mutations in Newly Identified Japanese Werner Syndrome Patients

Molecular Syndromology
Yoshiro MaezawaJunko Oshima

Abstract

Werner syndrome (WS) is a rare autosomal recessive disorder characterized by systemic accelerated aging. It is caused by pathogenic variants of the WRN gene that encodes a nuclear helicase. In this report, we describe 4 newly identified WS cases among those referred to the Japanese Werner Consortium, Chiba University, Japan. All 4 cases were compound heterozygotes of the Japanese founder mutation, c.3139-1G>C, and a novel null pathogenic variant, c.1587G>A, c.2448+1G>A, or c.3233+1G>T, or an amino acid substitution variant, c.1720G>A, p.Gly574Arg. These 3 null pathogenic variants were not previously described. The p. Gly574Arg was previously reported in a European patient, and the identification of the second p. Gly574Arg case, with classical WS features, further confirmed the pathogenic nature of this variant. For the case with c.3233+1G>T, we determined the phase of 2 disease-causing mutations and demonstrated that they are on different chromosomes. This assay would be particularly important for those cases with ambiguous clinical diagnosis.

References

May 29, 1999·Lancet·M SatohY Furuichi
May 5, 2006·Human Mutation·Shurong HuangJunko Oshima
Jun 21, 2006·Human Mutation·Nancy A UhrhammerYves-Jean Bignon
Apr 14, 2009·Nature Methods·Daniel G GibsonHamilton O Smith
Jul 24, 2012·Geriatrics & Gerontology International·Minoru TakemotoKoutaro Yokote
Apr 16, 2013·DNA Repair·Takashi TadokoroVilhelm A Bohr
Mar 13, 2014·Annual Review of Biochemistry·Deborah L CroteauVilhelm A Bohr
Mar 5, 2016·Cold Spring Harbor Perspectives in Medicine·Fuki M HisamaGeorge M Martin
Mar 20, 2016·Ageing Research Reviews·Junko OshimaRaymond J Monnat
Apr 11, 2017·Journal of the American Geriatrics Society·Masaya YamagaKoutaro Yokote
Oct 19, 2017·F1000Research·Raghavendra A ShamannaVilhelm A Bohr

❮ Previous
Next ❯

Citations

Nov 6, 2018·Molecular Genetics & Genomic Medicine·Forough SargolzaeiavalJunko Oshima

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.