Nijmegen breakage syndrome: clinical characteristics and mutation analysis in eight unrelated Russian families.
OBJECTIVE
The purpose of the study was to ascertain patients with Nijmegen breakage syndrome (NBS) in the Russian population and characterize the clinical phenotype and molecular genotype of these patients.


METHODS
Eight unrelated Russian patients with possible diagnoses of NBS were identified. Family histories were collected and clinical and laboratory analyses were carried out. Mutation screening of the NBS1 gene was carried out to confirm the diagnosis in 7 cases.


RESULTS
All patients had the key diagnostic features of NBS. One patient had acute myeloblastic leukemia (AML). Two patients had bone marrow aplasia, not previously described as a feature of NBS. Mutation screening of the NBS1 gene revealed that 6 patients were homozygous for the 657del5 mutation, whereas a seventh patient was a compound heterozygote, having the 657del5 mutation and an additional novel mutation, 681delT.


CONCLUSIONS
Molecular analyses confirmed the diagnosis of NBS in 7 of the patients. The surprising finding of bone marrow aplasia or AML in 3 of 7 patients raises the possibility of a connection between NBS and another DNA damage disorder, Fanconi anemia.
Resnick
Igor B
IB
Institute of Paediatric Hematology and the Institute of Clinical Genetics, Russian Federal Children's Hospital, Moscow, Russia.
Kondratenko
Irina
I
Togoev
Oleg
O
Vasserman
Natalia
N
Shagina
Irena
I
Evgrafov
Oleg
O
Tverskaya
Svetlana
S
Cerosaletti
Karen M
KM
Gatti
Richard A
RA
Concannon
Patrick
P
D002873:Chromosome Fragility; D005260:Female; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000235:genetics* / Q000276:immunology; D008831:Microcephaly / Q000235:genetics* / Q000276:immunology; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics; D010641:Phenotype; D012426:Russia; D013577:Syndrome
D009687:Nuclear Proteins