Definitive diagnosis of mandibular hypoplasia, deafness, progeroid features and lipodystrophy (MDPL) syndrome caused by a recurrent &lt;i&gt;de novo&lt;/i&gt; mutation in the &lt;i&gt;POLD1&lt;/i&gt; gene

Sasaki, Haruka; Yanagi, Kumiko; Ugi, Satoshi; Kobayashi, Kazuo; Ohkubo, Kumiko; Tajiri, Yuji; Maegawa, Hiroshi; Kashiwagi, Atsunori; Kaname, Tadashi

doi:10.1507/endocrj.ej17-0287

Cited by 46 publications

(35 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…17 A POLD1 heterozygous single-amino-acid deletion that maps to the catalytic domain and that abrogates the DNA polymerase but not exonuclease activity has been identified in patients with a developmental disorder of mandibular hypoplasia, sensorineural hearing loss, progeroid features, and lipodystrophy with insulin resistance. 18,19 Thus mutations affecting different domains of POLD1 give rise to distinct disorders and phenotypes.…”

mentioning

confidence: 99%

Combined immunodeficiency caused by a loss-of-function mutation in DNA polymerase delta 1

Cui

Keleş

Charbonnier

et al. 2020

Journal of Allergy and Clinical Immunology

View full text Add to dashboard Cite

Polyclonal T cell response Oligoclonal CD8 + T Cell response A human immunodeficiency-causing POLD1 mutation disrupts the Polδ δ complex and severely restricts polyclonal CD8 + T cell responses T cells PCNA: Proliferating Cell Nuclear Antigen Polδ: DNA polymerase delta POLD1: DNA polymerase delta 1 catalytic subunit POLD1 : POLD1 R1060C RFC: Replication Factor C Pan T cell lymphopenia Recurrent viral infections Background: Mutations affecting DNA polymerases have been implicated in genomic instability and cancer development, but the mechanisms by which they can affect the immune system remain largely unexplored. Objective: We sought to establish the role of DNA polymerase d1 catalytic subunit (POLD1) as the cause of a primary immunodeficiency in an extended kindred. Methods: We performed whole-exome and targeted gene sequencing, lymphocyte characterization, molecular and functional analyses of the DNA polymerase d (Pold) complex, and T-and B-cell antigen receptor repertoire analysis. Results: We identified a missense mutation (c. 3178C>T; p.R1060C) in POLD1 in 3 related subjects who presented with recurrent, especially herpetic, infections and T-cell lymphopenia with impaired T-cell but not B-cell proliferation. The mutation destabilizes the Pold complex, leading to ineffective recruitment of replication factor C to initiate DNA replication. Molecular dynamics simulation revealed that the R1060C mutation

show abstract

mentioning

confidence: 99%

Combined immunodeficiency caused by a loss-of-function mutation in DNA polymerase delta 1

Cui

Keleş

Charbonnier

et al. 2020

Journal of Allergy and Clinical Immunology

View full text Add to dashboard Cite

show abstract

“…The father and the brother were not included because consent was not obtained for them. Whole exome sequencing and analysis of the patient and his mother were performed as described previously (Sasaki et al, ). In brief, for exon capture and sequencing, the SureSelect Human All Exon V6 kit (Agilent Technology, Santa Clara, CA) and a HiSeq2500 (Illumina, San Diego, CA) with 125‐bp paired‐end reads were used, respectively.…”

Section: Methodsmentioning

confidence: 99%

Japanese patient with Cole‐carpenter syndrome with compound heterozygous variants of SEC24D

Takeyari

Kubota

Miyata

et al. 2018

American J of Med Genetics Pt A

Self Cite

View full text Add to dashboard Cite

Cole‐Carpenter syndrome is a rare skeletal dysplasia associated with low‐bone mass or an osteogenesis imperfecta (OI)‐like syndrome. Only 3 and 6 variants in SEC24D have been reported in patients with Cole‐Carpenter syndrome type 2 and autosomal recessive OI, respectively. We describe a 15‐year‐old Japanese boy with short stature of the short‐trunk type and craniofacial abnormalities including ocular proptosis, marked frontal bossing, midface hypoplasia, and micrognathia. These features were consistent with a diagnosis of Cole‐Carpenter syndrome. He had low‐bone mineral density and basilar impression. Whole exome sequencing analysis identified biallelic variants in SEC24D (p.Arg484* and p.Arg313His) in the patient. We will report a patient with compound heterozygous variants of SEC24D causing Cole‐Carpenter syndrome type 2.

show abstract

“…Moreover, many human homologous genes were identified in yeast as having roles in genetic instability, cancer progression, and accelerated aging [122]. For instance, mandibular hypoplasia, deafness, progeroid features, and lipodystrophy (MDPL) syndrome is a Werner-like progeroid syndrome characterized by osteoporosis, loss of hearing, early onset of diabetes, lipodystrophy, accelerated aging and steatosis [123]. Ruijs-Aalfs syndrome (RAS) is also characterized as a Werner-like progeroid syndrome, and its patients have grey hair, osteoporosis, diabetes, atherosclerosis, cataracts, sarcopenia, and cancer [123].…”

Section: Associating Aging With Genomic Instabilitymentioning

confidence: 99%

Insights into the Conserved Regulatory Mechanisms of Human and Yeast Aging

et al. 2020

View full text Add to dashboard Cite

Aging represents a significant biological process having strong associations with cancer, diabetes, and neurodegenerative and cardiovascular disorders, which leads to progressive loss of cellular functions and viability. Astonishingly, age-related disorders share several genetic and molecular mechanisms with the normal aging process. Over the last three decades, budding yeast Saccharomyces cerevisiae has emerged as a powerful yet simple model organism for aging research. Genetic approaches using yeast RLS have led to the identification of hundreds of genes impacting lifespan in higher eukaryotes. Numerous interventions to extend yeast lifespan showed an analogous outcome in multi-cellular eukaryotes like fruit flies, nematodes, rodents, and humans. We collected and analyzed a multitude of observations from published literature and provide the contribution of yeast in the understanding of aging hallmarks most applicable to humans. Here, we discuss key pathways and molecular mechanisms that underpin the evolutionarily conserved aging process and summarize the current understanding and clinical applicability of its trajectories. Gathering critical information on aging biology would pave the way for future investigation targeted at the discovery of aging interventions.

show abstract

Definitive diagnosis of mandibular hypoplasia, deafness, progeroid features and lipodystrophy (MDPL) syndrome caused by a recurrent <i>de novo</i> mutation in the <i>POLD1</i> gene

Cited by 46 publications

References 38 publications

Combined immunodeficiency caused by a loss-of-function mutation in DNA polymerase delta 1

Combined immunodeficiency caused by a loss-of-function mutation in DNA polymerase delta 1

Japanese patient with Cole‐carpenter syndrome with compound heterozygous variants of SEC24D

Insights into the Conserved Regulatory Mechanisms of Human and Yeast Aging

Contact Info

Product

Resources

About