DNA Damage as a Driver for Growth Delay: Chromosome Instability Syndromes with Intrauterine Growth Retardation

Teresa, Benilde García-de; Hernández-Gómez, Mariana; Frı́as, Sara

doi:10.1155/2017/8193892

Cited by 19 publications

(14 citation statements)

References 78 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Most frequent syndromes are summarized in Table . Some of these syndromes derive from an impairment in DNA repair, causing chromosome instability syndromes . They include Fanconi anemia, Seckel, Bloom and Nijmegen Breakage Syndromes, all with an autosomal recessive inheritance pattern.…”

Section: Monogenic Disordersmentioning

confidence: 99%

Genetic syndromes associated with isolated fetal growth restriction

2020

View full text Add to dashboard Cite

Early onset fetal growth restriction (FGR) may be due to impaired placentation, environmental or toxic exposure, congenital infections or genetic abnormalities. Remarkable research, mainly based on retrospective series, has been published on the diverse genetic causes. Those have become more and more relevant with the improvement in the accuracy of the analysis techniques and the rising of breakthrough genomewide methods such as the whole genome sequencing. However, no publication has presented an integrated view of management of those fetuses with an early and severe affection. In this review, we explored to which extent genetic syndromes can cause FGR fetuses without structural defects. The most common chromosomal abnormalities (Triploidies and Trisomy 18), submicroscopic chromosomal anomalies (22q11.2 microduplication syndrome) and single gene disorders (often associated with mild ultrasound findings) related to early and severe FGR had been analysed. Finally, we addressed the impact of epigenetic marks on fetal growth, a matter of growing importance. At the end of this review, we should be able to provide an adequate counseling to parents in terms of diagnosis, prognosis and management of those pregnancies.

show abstract

Section: Monogenic Disordersmentioning

confidence: 99%

Genetic syndromes associated with isolated fetal growth restriction

2020

View full text Add to dashboard Cite

show abstract

“…The association to genes from the downstream part of the FA/BRCA pathway has also been found for a small head; microcephaly, described in almost 30% of published cases [8], may reflect the importance of appropriate DNA repair in neural progenitors undergoing rapid replication cycles during central nervous system development [83,84].…”

Section: Development Alterationsmentioning

confidence: 83%

Chromosome Instability in Fanconi Anemia: From Breaks to Phenotypic Consequences

García-de-Teresa

Rodríguez

Frı́as

2020

Preprint

View full text Add to dashboard Cite

Fanconi anemia (FA), a chromosomal instability syndrome, is caused by inherited pathogenic variants in any of 22 FANC genes, that cooperate in the FA/BRCA pathway. This pathway regulates the repair of DNA interstrand crosslinks (ICLs) through homologous recombination. In FA proper repair of ICLs is impaired, and accumulation of toxic DNA double strand breaks occurs. In order to repair this type of DNA damage, FA cells activate alternative error-prone DNA repair pathways, that may lead to the formation of gross structural chromosome aberrations of which radial figures are the hallmark of FA and their segregation during cell division are the origin of subsequent aberrations like translocations, dicentrics and acentric fragments. The deficiency in DNA repair has pleiotropic consequences in the phenotype of patients with FA, including developmental alterations, bone marrow failure and an extreme risk to develop cancer. The mechanisms leading to the physical abnormalities during embryonic development have not been clearly elucidated, however FA has features of premature aging with chronic inflammation mediated by pro-inflammatory cytokines, that results in tissue attrition, selection of malignant clones and cancer onset. Moreover, the effect of the FA/BRCA pathway in germinal cells, evidenced by infertility in patients with FA attests of chromosomal instability and cell death also occurring in the germinal compartment.

show abstract

“…24,25 DNA damage response (DDR) is a particular way of the DNA repair mechanism involved in lesions detection, signaling, and repair promotion as well as cell cycle progression control. 26 Changes in DDR shows DNA damage and subsequent genomic instability, cell cycle deregulation that ensues overgrowth and cellular apoptosis. 24 Dysfunction of DDR is a remarkable feature in pathophysiological mechanisms of the chromosome instability syndromes.…”

Section: Pathophysiological Mechanisms and Geneticsmentioning

confidence: 99%

Beyond Typical Ataxia Telangiectasia: How to Identify the Ataxia Telangiectasia‐Like Disorders

Raslan

Matos

Ciarlariello

et al. 2020

Movement Disord Clin Pract

View full text Add to dashboard Cite

Background Background: Ataxia telangiectasia is one of the most common causes of autosomal recessive cerebellar ataxias. However, absence of telangiectasia, normal levels of alpha-fetoprotein and negative genetic test may direct to alternative diagnosis with similar phenotypes such as ataxia telangiectasia-like disorders (ATLD). Cases Cases: We report two instructive cases of ATLD: the first case with ataxia telangiectasia-like disorder type 1 related to MRE11A gene, and the second case with ataxia telangiectasia-like disorder type 2 related to PCNA gene. Literature Review Literature Review: ATLD is an unusual group of autosomal recessive diseases that share some clinical features and pathophysiological mechanisms with ataxia telangiectasia (AT). ATLD may be associated with mutations in the MRE11A (ATLD type 1) and PCNA (ATLD type 2) genes. ATLD belongs to the group of chromosomal instability syndromes. The reason for the term ATLD is related to the similar pathophysiological mechanisms observed in AT, which is characterized by chromosomal instability and radiosensitivity. Conclusions Conclusions: In this review, the main clinical features, biomarkers, brain imaging and genetics of ATLD are discussed. Mutations in the MRE11A and PCNA genes should be included in the differential diagnosis for early onset cerebellar ataxia with absence of telangiectasia and normal levels of alpha-fetoprotein.

show abstract

DNA Damage as a Driver for Growth Delay: Chromosome Instability Syndromes with Intrauterine Growth Retardation

Cited by 19 publications

References 78 publications

Genetic syndromes associated with isolated fetal growth restriction

Genetic syndromes associated with isolated fetal growth restriction

Chromosome Instability in Fanconi Anemia: From Breaks to Phenotypic Consequences

Beyond Typical Ataxia Telangiectasia: How to Identify the Ataxia Telangiectasia‐Like Disorders

Contact Info

Product

Resources

About