Academic Journal
Monoallelic BUB1B mutations and defective mitotic‐spindle checkpoint in seven families with premature chromatid separation (PCS) syndrome
| العنوان: | Monoallelic BUB1B mutations and defective mitotic‐spindle checkpoint in seven families with premature chromatid separation (PCS) syndrome |
|---|---|
| المؤلفون: | Matsuura, Shinya, Matsumoto, Yoshiyuki, Morishima, Ken‐ichi, Izumi, Hideki, Matsumoto, Hiroshi, Ito, Emi, Tsutsui, Keisuke, Kobayashi, Junya, Tauchi, Hiroshi, Kajiwara, Yoshinori, Hama, Seiji, Kurisu, Kaoru, Tahara, Hidetoshi, Oshimura, Mitsuo, Komatsu, Kenshi, Ikeuchi, Tatsuro, Kajii, Tadashi |
| المصدر: | American Journal of Medical Genetics Part A ; volume 140A, issue 4, page 358-367 ; ISSN 1552-4825 1552-4833 |
| بيانات النشر: | Wiley |
| سنة النشر: | 2006 |
| المجموعة: | Wiley Online Library (Open Access Articles via Crossref) |
| الوصف: | Cancer‐prone syndrome of premature chromatid separation (PCS syndrome) with mosaic variegated aneuploidy (MVA) is a rare autosomal recessive disorder characterized by growth retardation, microcephaly, childhood cancer, premature chromatid separation of all chromosomes, and mosaicism for various trisomies and monosomies. Biallelic BUB1B mutations were recently reported in five of eight families with MVA syndrome (probably identical to the PCS syndrome). We here describe molecular analysis of BUB1B (encoding BubR1) in seven Japanese families with the PCS syndrome. Monoallelic BUB1B mutations were found in all seven families studied: a single‐base deletion (1833delT) in four families; and a splice site mutation, a nonsense mutation, and a missense mutation in one family each. Transcripts derived from the patients with the 1833delT mutation and the splice site mutation were significantly reduced, probably due to nonsense‐mediated mRNA decay. No mutation was found in the second alleles in the seven families studied, but RT‐PCR of BUB1B and Western blot analysis of BubR1 indicated a modest decrease of their transcripts. BubR1 in the cells from two patients showed both reduced protein expression and diminished kinetochore localization. Their expression level of p55cdc, a specific activator of anaphase‐promoting complex, was normal but its kinetochore association was abolished. Microcell‐mediated transfer of chromosome 15 (containing BUB1B ) into the cells restored normal BubR1 levels, kinetochore localization of p55cdc, and the normal responses to colcemid treatment. These findings indicate the involvement of BubR1 in p55cdc‐mediated mitotic checkpoint signaling, and suggest that >50% decrease in expression (or activity) of BubR1 is involved in the PCS syndrome. © 2006 Wiley‐Liss, Inc. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1002/ajmg.a.31069 |
| الاتاحة: | http://dx.doi.org/10.1002/ajmg.a.31069 https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fajmg.a.31069 https://onlinelibrary.wiley.com/doi/pdf/10.1002/ajmg.a.31069 |
| Rights: | http://onlinelibrary.wiley.com/termsAndConditions#vor |
| رقم الانضمام: | edsbas.56C669F7 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1002/ajmg.a.31069 |
|---|