Clinical ascertainment of Nijmegen breakage syndrome (NBS) and prevalence of the major mutation, 657del5, in three Slav populations

Varon, Raymonda; Seemanová, E; Chrzanowska, Krystyna; Hnateyko, Oleg; Piekutowska‐Abramczuk, Dorota; Krajewska‐Walasek, M; Sykut-Cegielska, Jolanta; Sperling, Karl; Reis, André

doi:10.1038/sj.ejhg.5200554

Cited by 137 publications

(106 citation statements)

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“…The frequency of 657del5 mutation carriers is relatively high in Slavic populations, reaching 1/177 in southern and 1/162 in central regions of Poland. (10,23) In contrast to our study, three 657del5 mutation carriers with cancer, described by Steffen et al, (23,27) had developed a second primary tumor. Recent findings for large groups of Polish patients strongly suggest the elevated risk of sporadic lymphoid malignancies (ALL 3/270 and NHL 2/212), (29) NHL (6/186), especially of the gastrointestinal tract, (28) and breast cancer (11/562) (27) in heterozygous 657del5 mutation carriers.…”

Section: Discussioncontrasting

confidence: 99%

“…NBS is a rare autosomal recessive disorder, occurring mainly in central and eastern Europe. (10) The most common is the homozygous 657del5 mutation, observed in 90% of NBS patients. The protein product of the NBS1 gene, nibrin (p95, NBS1), is a member of the MRE11-RAD50-nibrin complex, (7) which is involved in DNA double-strand break repair by homologous recombination or non-homologous end joining, meiotic recombination and the DNA damage response.…”

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Increased risk of larynx cancer in heterozygous carriers of the I171V mutation of the NBS1 gene

Ziółkowska

Mosor

Wierzbicka³

et al. 2007

Cancer Science

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The high incidence of multiple primary tumors (MPT) is a significant problem in head and neck tumor treatment. Recent studies suggest that carriers of heterozygous mutations in the NBS1 gene have an increased risk of malignant tumor development. The aim of our research was to assess the frequency of NBS1 mutations in patients with larynx cancer only (LC) and with MPT. The MPT group consisted of patients with one cancer localized to the larynx (primary or second) and another at another site. DNA from 175 patients with LC and 93 patients with MPT was analyzed using the single-strand conformation polymorphism method and direct sequencing. We found nine carriers of the I171V mutation among these 268 cancer patients and only one carrier among 500 population controls (0.2%). Four carriers of the I171V mutation were detected among 175 LC patients (2.3%) and five among 93 patients with MPT (5.4%). The frequencies of the I171V mutation carriers in LC and MPT patients were significantly higher than in controls (odds ratio D espite recent advances in the diagnosis and treatment of head and neck squamous cell carcinoma (HNSCC), the survival rate of patients with these tumors is not improving. One of the reasons for this is the frequent development of second primary tumors (SPT). Among HNSCC patients, the frequency of SPT occurrence ranges from 12 to 30% with a constant rate of 2-3% per year for patients who survive for more than 10 years.[(1-3) The first tumor is responsible for 15% of patient deaths, whereas the second tumor is the cause of death in 71% of cases. Squamous cell carcinoma is the predominant histological type of the second tumor. (4) In the etiology of multiple primary tumors (MPT) of the head and neck, tobacco and alcohol abuse ('condemned mucosa theory') are essential but are not the only causal factors.(5) It is supposed that genetic factors play a great role in the occurrence of the first tumor and, in addition, predispose the patient to the development of a second primary tumor. Because of reduced DNA repair capacity in patients who had two or more independent malignancies, (6) it has been suggested that alterations in DNA repair genes may play a significant role in head and neck tumor development.The NBS1 gene belongs to a group of double-strand break repair genes and is located on chromosome band 8q21.3. (7)(8)(9) Biallelic mutations in the NBS1 gene are responsible for Nijmegen breakage syndrome (NBS, OMIM 251260), classified to a group of chromosomal instability syndromes. NBS is a rare autosomal recessive disorder, occurring mainly in central and eastern Europe.(10) The most common is the homozygous 657del5 mutation, observed in 90% of NBS patients. The protein product of the NBS1 gene, nibrin (p95, NBS1), is a member of the MRE11-RAD50-nibrin complex, (7) which is involved in DNA double-strand break repair by homologous recombination or non-homologous end joining, meiotic recombination and the DNA damage response. (7,11) The MRE11-RAD50-nibrin complex is also required for activation of the damage c...

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Section: Discussioncontrasting

confidence: 99%

mentioning

confidence: 99%

Increased risk of larynx cancer in heterozygous carriers of the I171V mutation of the NBS1 gene

Ziółkowska

Mosor

Wierzbicka³

et al. 2007

Cancer Science

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“…After the first clinical recognition of the disorder, NBS sufferers appeared to be prevalent among eastern and central European populations, particularly in Poland, and at least 90 patients have been included in the International NBS Registry (INR). The incidence of NBS heterozygotes is estimated 1/177 in Polish, Czech and Ukrainian groups (Varon et al, 2000). Patients with NBS have early and proportional growth retardation, and progressive and severe microcephaly after the first months of life (Table 1).…”

Section: Introductionmentioning

confidence: 99%

Nijmegen breakage syndrome gene, NBS1, and molecular links to factors for genome stability

et al. 2002

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DNA double-strand breaks represent the most potentially serious damage to a genome and hence, at least two pathways of DNA repair have evolved; namely, homologous recombination repair and non-homologous end joining. Defects in both rejoining processes result in genomic instability including chromosome rearrangements, LOH and gene mutations, which may lead to development of malignancies. Nijmegen breakage syndrome is a recessive genetic disorder, characterized by elevated sensitivity to ionizing radiation that induces double-strand breaks, and high frequency of malignancies. NBS1, the product of the gene underlying the disease, forms a multimeric complex with hMRE11/ hRAD50 nuclease and recruits them to the vicinity of sites of DNA damage by direct binding to phosphorylated histone H2AX. The combination of the highlyconserved NBS1 forkhead associated domain and BRCA1 C-terminus domain has a crucial role for recognition of damaged sites. Thereafter, the NBS1-complex proceeds to rejoin double-strand breaks predominantly by homologous recombination repair in vertebrates. This process collaborates with cell-cycle checkpoints at S and G2 phase to facilitate DNA repair. NBS1 is also associated with telomere maintenance and DNA replication. Based on recent knowledge regarding NBS1, we propose here a two-step binding mechanism for damage recognition by repair proteins, and describe the molecular links to factors for genome stability.

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“…Nijmegen Breakage Sendromu (NBS), nadir görülen mikrosefali, tipik yüz görünümü (kuş yüzü), büyüme geriliği, mental retardasyon, immün yetmezlik, radyasyon duyarlılığı ve artmış lenfoid malignite riski ile karakterize bir kromozomal instabilite hastalığıdır (1,2). Gerçek insidansı bilinmemekle birlikte etnik olarak daha çok Doğu Avrupa, özellikle Polonya ve Çekoslovakya'da sık görülen bir hastalıktır (1,3).…”

Section: Introductionunclassified

“…Gerçek insidansı bilinmemekle birlikte etnik olarak daha çok Doğu Avrupa, özellikle Polonya ve Çekoslovakya'da sık görülen bir hastalıktır (1,3). İlk olarak 1981 yılında Hollandalı hastalarda tanımlanan; ve otozomal resesif kalıtılan NBS, 8 nolu kromozomda bulunan (8q21) ve nibrin proteinini kodlayan NBS1 geninde mutasyon sonucu ortaya çıkar (4).…”

Section: Introductionunclassified

Nijmegen Breakage Sendromlu Bir Olgunun Uzun Süreli izlemi

Yüzüak¹,

Göktürk²,

Sayar³

et al. 2017

Asthma Allergy Immunol

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Clinical ascertainment of Nijmegen breakage syndrome (NBS) and prevalence of the major mutation, 657del5, in three Slav populations

Cited by 137 publications

References 9 publications

Increased risk of larynx cancer in heterozygous carriers of the I171V mutation of the NBS1 gene

Increased risk of larynx cancer in heterozygous carriers of the I171V mutation of the NBS1 gene

Nijmegen breakage syndrome gene, NBS1, and molecular links to factors for genome stability

Nijmegen Breakage Sendromlu Bir Olgunun Uzun Süreli izlemi

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