Nijmegen breakage syndrome

Background-Nijmegen breakage syndrome (NBS) is a rare autosomal recessive d isorder. NBS-1, the gene defective in NBS, is located on chromosome 8q21 an d has recently been cloned. The gene product, nibrin, is a novel protein, w hich is member of the hMre11/hRad50 protein complex, suggesting that the ge ne is involved in DNA double strand break repair. Aims-To study the clinical and laboratory features of NBS as well as the ge notype-phenotype relation. Methods-Fifty five patients with NBS, included in the NBS registry in Nijme gen were evaluated. The majority of the patients were of eastern European a ncestry. Most of them had shown a truncating 5 bp deletion 657-661 deLACAAA . Four further truncating mutations have been identified in patients with o ther distinct haplotypes. Results and conclusions-Essential features found in NBS were microcephaly, usually without severe retardation, typical facial appearance, immunodefici ency, chromosomal instability, x ray hypersensitivity, and predisposition t o malignancy. In 40% of the patients cancer was noted before the age of 21 years. Important additional features were skin abnormalities, particularly cafe au lait spots and vitiligo, and congenital malformations, particularly clinodactyly and syndactyly. Congenital malformations, immunodeficiency, r adiation hypersensitivity, and cancer predispostion were comprehensible in case of dysfunctioning of DNA repair mechanisms. No specific genotype-pheno type relation could be found. Patients with the same genotype may show diff erent phenotypes and patients with different genotypes may express the same phenotype. Specific mutations did not lead to specific clinical features.