Nijmegen breakage syndrome: case report and review of literature

Hasbaoui, Brahim El; Elyajouri, Abdelhkim; Abilkassem, R.; Agadr, Aomar

doi:10.11604/pamj.2020.35.85.14746

Cited by 16 publications

(11 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Mutations that disrupt DDR pathways cause diseases with neurological symptoms and are usually accompanied by increased cancer risk or immunological deficiencies, e.g., Nijmegen breakage syndrome associated with mutations in NBS1, part of the MRN complex that processes DSBs in both HR and NHEJ pathways 63 , and mutations in the NHEJ ligase LIG4 64 . Many patients with these syndromes exhibit microcephaly, which indicates that the impaired DNA repair strongly affects NPC proliferation.…”

Section: Discussionmentioning

confidence: 99%

The neurodevelopmental disorder-linked PHF14 complex that forms biomolecular condensates detects DNA damage and promotes repair

Käsper¹,

Hwang²,

Fung³

et al. 2021

Preprint

View full text Add to dashboard Cite

Numerous chromatin-associated proteins have been linked to neurodevelopmental disorders, yet their molecular functions often remain elusive. PHF14, HMG20A, TCF20 and RAI1 are components of a putative chromatin-associated complex and have been implicated in neurological disorders. Here, we found that Phf14 knockout embryonic stem cells and neural progenitor cells exhibit impaired cell cycle progression and proliferation, inadequate protection of stalled replication forks, and decreased DNA repair. The PHF14 complex rapidly assembles at DNA damage sites and binds to DNA through HMG20A. The PHF14 complex forms DNA-containing phase separated droplets in vitro, where TCF20 facilitates droplet formation. Furthermore, TCF20 maintenance at DNA damage sites is destabilized upon pathological mutation. Our results suggest that the PHF14 complex contributes to DNA damage repair by sensing damaged sites and forming biomolecular condensates, thus supporting cell cycle progression, especially in neural progenitor cells whose spatiotemporal pool is critical for proper brain development.

show abstract

Section: Discussionmentioning

confidence: 99%

The neurodevelopmental disorder-linked PHF14 complex that forms biomolecular condensates detects DNA damage and promotes repair

Käsper¹,

Hwang²,

Fung³

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…Nijmegen breakage syndrome is an autosomal recessive chromosomal instability syndrome with an overall prevalence estimated at 1:100 000, whereas it is more common in Eastern Europe with an estimated carrier frequency of 1:177 in Slav populations 118,119 . The phenotype typically encompasses progressive microcephaly, pre‐ and postnatal growth retardation, immunodeficiency with recurrent infections, and predisposition to cancer, specifically mainly non‐Hodgkin lymphoma, but also medulloblastoma, glioma, and rhabdomyosarcoma.…”

Section: Pathogenesis and Clinical Phenotypes Of Selected Premature Amentioning

confidence: 99%

“…Nijmegen breakage syndrome is caused by biallelic loss‐of‐function mutations in NBN with the majority of patients carrying the founder mutation c.657_661del5 (p.Lys219Asnfs). NBN is coding for nibrin, which interacts with ATM in DDR and DNA repair 118 …”

Section: Pathogenesis and Clinical Phenotypes Of Selected Premature Amentioning

confidence: 99%

Premature aging disorders: A clinical and genetic compendium

2020

View full text Add to dashboard Cite

Progeroid disorders make up a heterogeneous group of very rare hereditary diseases characterized by clinical signs that often mimic physiological aging in a premature manner. Apart from Hutchinson-Gilford progeria syndrome, one of the bestinvestigated progeroid disorders, a wide spectrum of other premature aging phenotypes exist, which differ significantly in their clinical presentation and molecular pathogenesis. Next-generation sequencing (NGS)-based approaches have made it feasible to determine the molecular diagnosis in the early stages of a disease. Nevertheless, a broad clinical knowledge on these disorders and their associated symptoms is still fundamental for a comprehensive patient management and for the interpretation of variants of unknown significance from NGS data sets. This review provides a detailed overview on characteristic clinical features and underlying molecular genetics of well-known as well as only recently identified premature aging disorders and also highlights novel findings towards future therapeutic options. K E Y W O R D S characteristic clinical features, hereditary, premature aging, progeroid disorders 1 | INTRODUCTION Aging is a general biological phenomenon that affects all human beings and results in a functional decline of physiological systems accompanied by an increased risk for chronic ailments with advancing chronological age. 1,2 At the molecular level, aging is for example associated with genomic instability, loss of heterochromatin, and the accumulation of macromolecular damage leading to reduced (stem) cell function and tissue regeneration. 3 Progeroid disorders show many clinical features of aging-associated pathologies and signs similar to physiological aging; however, they occur at earlier ages and often progress rapidly. In many aspects progeria therefore represents a timelapse form of aging. Premature aging processes are mostly segmental in that they involve one or more organs, but do not exhibit all aspects associated with physiological aging. Premature aging signs include, among others, alopecia, hair graying, lipodystrophy, osteoporosis, joint contractures, cataract, hearing loss, atherosclerosis, cardiovascular diseases, diabetes mellitus and malignancies at an early age. In addition to these typical aging phenotypes, progeria patients may also present with growth retardation, developmental delay, and intellectual disability. A more modular view of segmental premature aging syndromes hypothesizes that a cluster of symptoms appearing in several disorders might be due to a common underlying cause-for example, alopecia, osteoporosis and nail atrophy have been proposed to be related to telomere shortening. 4 Research into premature aging disorders aims at understanding the pathogenesis and to develop novel treatment strategies, but also intends to unshadow physiological aging processes since premature aging phenotypes mirror many of the clinical aspects of physiological aging. 3 One of the best-known premature aging disorders is the Hutchinson-Gilford progeria syndr...

show abstract

“…The hallmark of NBS is microcephaly, usually since birth, with normal or mildly impaired psychomotor development. Other cardinal features include a typical facial appearance with a prominent midface, recurrent respiratory infections, chromosomal instability, radiation hypersensitivity, and predisposition to malignancy [ 30 , 33 ]. Some patients may also have café au lait spots, clinodactyly and syndactyly.…”

Section: Nijmegen Breakage Syndromementioning

confidence: 99%

Infections in DNA Repair Defects

Demirdağ

Gupta

2023

Pathogens

View full text Add to dashboard Cite

DNA repair defects are heterogenous conditions characterized by a wide spectrum of clinical phenotypes. The common presentations of DNA repair defects include increased risk of cancer, accelerated aging, and defects in the development of various organs and systems. The immune system can be affected in a subset of these disorders leading to susceptibility to infections and autoimmunity. Infections in DNA repair defects may occur due to primary defects in T, B, or NK cells and other factors such as anatomic defects, neurologic disorders, or during chemotherapy. Consequently, the characteristics of the infections may vary from mild upper respiratory tract infections to severe, opportunistic, and even fatal infections with bacteria, viruses, or fungi. Here, infections in 15 rare and sporadic DNA repair defects that are associated with immunodeficiencies are discussed. Because of the rarity of some of these conditions, limited information is available regarding infectious complications.

show abstract

Nijmegen breakage syndrome: case report and review of literature

Cited by 16 publications

References 15 publications

The neurodevelopmental disorder-linked PHF14 complex that forms biomolecular condensates detects DNA damage and promotes repair

The neurodevelopmental disorder-linked PHF14 complex that forms biomolecular condensates detects DNA damage and promotes repair

Premature aging disorders: A clinical and genetic compendium

Infections in DNA Repair Defects

Contact Info

Product

Resources

About