Rare presentation of Rothmund-Thomson syndrome with novel compound heterozygous mutations of the RECQL4 gene

Zhang, Xinyue; Geng, Songmei; Zheng, Yi

doi:10.1016/j.abd.2019.10.006

Cited by 2 publications

(1 citation statement)

References 5 publications

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“…In addition to the symptoms that RTS has in common with Bloom syndrome, Werner syndrome, BGS and RAPADILINO, RTS individuals can also have photosensitivity with poikiloderma, graying hair, alopecia, hyperpigmented patches, telangiectasias, dystrophic teeth and dystrophic nails [ 112 , 113 , 118 , 121 , 122 , 187 , 190 , 191 , 192 , 193 ]. Many unique genetic variants have been demonstrated to be causative for RTS [ 112 , 113 , 117 , 123 , 124 , 125 , 126 , 127 , 128 , 129 , 130 , 131 , 132 , 133 , 134 , 135 , 136 , 137 , 138 , 139 , 187 , 191 ]. Patients afflicted with RTS usually have compound heterozygous mutations in RECQL4 with at least one nonsense mutation that causes a truncation, either deleting or disrupting the helicase domain ( Figure 8 and Supplementary Table S1 ) [ 112 , 118 , 120 ].…”

Section: Diseasesmentioning

confidence: 99%

Congenital Diseases of DNA Replication: Clinical Phenotypes and Molecular Mechanisms

Schmit

Bielinsky

2021

IJMS

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Deoxyribonucleic acid (DNA) replication can be divided into three major steps: initiation, elongation and termination. Each time a human cell divides, these steps must be reiteratively carried out. Disruption of DNA replication can lead to genomic instability, with the accumulation of point mutations or larger chromosomal anomalies such as rearrangements. While cancer is the most common class of disease associated with genomic instability, several congenital diseases with dysfunctional DNA replication give rise to similar DNA alterations. In this review, we discuss all congenital diseases that arise from pathogenic variants in essential replication genes across the spectrum of aberrant replisome assembly, origin activation and DNA synthesis. For each of these conditions, we describe their clinical phenotypes as well as molecular studies aimed at determining the functional mechanisms of disease, including the assessment of genomic stability. By comparing and contrasting these diseases, we hope to illuminate how the disruption of DNA replication at distinct steps affects human health in a surprisingly cell-type-specific manner.

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Section: Diseasesmentioning

confidence: 99%

Congenital Diseases of DNA Replication: Clinical Phenotypes and Molecular Mechanisms

Schmit

Bielinsky

2021

IJMS

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Molecular Mechanisms of the RECQ4 Pathogenic Mutations

Chang

Min

et al. 2021

Front. Mol. Biosci.

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The human RECQ4 gene encodes an ATP-dependent DNA helicase that contains a conserved superfamily II helicase domain located at the center of the polypeptide. RECQ4 is one of the five RECQ homologs in human cells, and its helicase domain is flanked by the unique amino and carboxyl termini with sequences distinct from other members of the RECQ helicases. Since the identification of the RECQ4 gene in 1998, multiple RECQ4 mutations have been linked to the pathogenesis of three clinical diseases, which are Rothmund-Thomson syndrome, Baller-Gerold syndrome, and RAPADILINO. Patients with these diseases show various developmental abnormalities. In addition, a subset of RECQ4 mutations are associated with high cancer risks, especially for osteosarcoma and/or lymphoma at early ages. The discovery of clinically relevant RECQ4 mutations leads to intriguing questions: how is the RECQ4 helicase responsible for preventing multiple clinical syndromes? What are the mechanisms by which the RECQ4 disease mutations cause tissue abnormalities and drive cancer formation? Furthermore, RECQ4 is highly overexpressed in many cancer types, raising the question whether RECQ4 acts not only as a tumor suppressor but also an oncogene that can be a potential new therapeutic target. Defining the molecular dysfunctions of different RECQ4 disease mutations is imperative to improving our understanding of the complexity of RECQ4 clinical phenotypes and the dynamic roles of RECQ4 in cancer development and prevention. We will review recent progress in examining the molecular and biochemical properties of the different domains of the RECQ4 protein. We will shed light on how the dynamic roles of RECQ4 in human cells may contribute to the complexity of RECQ4 clinical phenotypes.

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Rare presentation of Rothmund-Thomson syndrome with novel compound heterozygous mutations of the RECQL4 gene

Cited by 2 publications

References 5 publications

Congenital Diseases of DNA Replication: Clinical Phenotypes and Molecular Mechanisms

Congenital Diseases of DNA Replication: Clinical Phenotypes and Molecular Mechanisms

Molecular Mechanisms of the RECQ4 Pathogenic Mutations

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