First case of aplastic anemia in a Japanese child with a homozygous missense mutation in theNBS1gene (I171V) associated with genomic instability.

Autor: Shimada, Hiroyuki, Shimizu, Kimiko, Mimaki, Sachiyo, Sakiyama, Tokuki, Mori, Tetsuya, Shimasaki, Noriko, Yokota, Jun, Nakachi, Kei, Ohta, Tsutomu, Ohki, Misao
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Zdroj: Human Genetics; Oct2004, Vol. 115 Issue 5, p372-376, 5p
Abstrakt: TheNBS1gene is strongly linked to several factors involved in genome integrity. Functional disruption of NBS1 could therefore induce genomic instability and carcinogenesis. Four children with acute lymphoblastic leukemia have been reported to be heterozygous for a germline and/or somatic missense mutation inNBS1, leading to the I171V substitution. We screened healthy controls and pediatric patients with hematological malignancies and aplastic anemia (AA) for the presence of I171V. Of the 62 patients, one individual with AA was confirmed to harbor a homozygous I171V mutation. Genetic analysis ofNBS1in this patient and her healthy parents indicated that she inherited the germline I171V mutation from her father and the wild-type allele from her mother, and that the second I171V hit occurred on the wild-type allele early in embryonic development. Furthermore, cytogenetic analysis of lymphoblastic cell lines from the patient indicated a remarkable increase in numerical and structural chromosomal aberrations in the absence of clastogens, suggesting that she potentially carried genomic instability. This is the first report of AA with a homozygous I171V mutation. We hypothesize thatNBS1may play an important role in the pathogenesis of AA. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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