657del5 mutation in the gene for Nijmegen breakage syndrome (NBS1) in a cohort of Russian children with lymphoid tissue malignancies and controls.
Nijmegen breakage syndrome (NBS, OMIM 251260) is a rare hereditary disease, characterized by immune deficiency, microcephaly, and an extremely high incidence of lymphoid tissue malignancies. The gene mutated in NBS, NBS1, was recently cloned from its location on chromosome 8q21. The encoded protein, nibrin (p95), together with hMre11 and hRad50, is involved in the double-strand DNA break repair system. We screened two Russian cohorts for the 657del5 NBS1 mutation and found no carriers in 548 controls and two carriers in 68 patients with lymphoid malignancies: one with acute lymphoblastic leukemia (ALL) and one with non-Hodgkin lymphoma (NHL). Several relatives of the second patient, who were carriers of the same mutation, had cancer (ALL, breast cancer, GI cancers). These preliminary data suggest that NBS1 mutation carriers can be predisposed to malignant disorders.
Resnick
Igor B
IB
Department of Immunology, Research Institute for Paediatric Hematology, Moscow, Russia. gashka@hadassah.org.il
Kondratenko
Irina
I
Pashanov
Eugeni
E
Maschan
Alexey A
AA
Karachunsky
Alexander
A
Togoev
Oleg
O
Timakov
Andrey
A
Polyakov
Alexander
A
Tverskaya
Svetlana
S
Evgrafov
Oleg
O
Roumiantsev
Alexander G
AG
D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D019457:Chromosome Breakage / Q000235:genetics*; D002898:Chromosomes, Human, Pair 8; D015331:Cohort Studies; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006579:Heterozygote; D006801:Humans; D019656:Loss of Heterozygosity; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics / Q000473:pathology; D008232:Lymphoproliferative Disorders / Q000235:genetics* / Q000473:pathology*; D008297:Male; D009154:Mutation; D010375:Pedigree; D010865:Pilot Projects; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000473:pathology; D012426:Russia; D017384:Sequence Deletion; D013577:Syndrome