X-linked VACTERL with hydrocephalus syndrome: further delineation of the phenotype caused by FANCB mutations.

X-linked VACTERL-hydrocephalus syndrome (X-linked VACTERL-H) is a rare disorder caused by mutations in the gene FANCB which underlies Fanconi Anemia (FA) complementation group B. Cells from affected males have increased chromosome breakage on exposure to DNA cross-linking agents. Only five FANCB mutations found in six affected males, including an affected uncle and nephew, have been reported. We have identified FANCB mutations in a further four affected families. The VACTERL-H phenotype segregates as an X-linked recessive trait in three of these. Each mutation is predicted to truncate the FANCB open reading frame and results in highly skewed X-inactivation in unaffected carrier females. Phenotypic data were available on six affected males. Comparison of the clinical findings in our patients with published clinical data (total 12 patients) shows that ventriculomegaly, bilateral absent thumbs and radii, vertebral defects, renal agenesis, and growth retardation are the major phenotypic signs in affected males. Less frequent are brain, pituitary, ear and eye malformations, gastrointestinal atresias (esophageal, duodenal and anal), tracheoesophageal fistula, lung segmentation defects, and small genitalia. Three of six of our patients survived the perinatal period. One boy lived up to 2 years 10 months but developed aplastic anemia and died of renal failure. These data show that loss-of-function FANCB mutations result in a recognizable, multiple malformation phenotype in hemizygous males for which we propose clinical criteria to aid diagnosis.

Mutation of the RAD51C gene in a Fanconi anemia-like disorder.

Fanconi anemia (FA) is a rare chromosomal-instability disorder associated with a variety of developmental abnormalities, bone marrow failure and predisposition to leukemia and other cancers. We have identified a homozygous missense mutation in the RAD51C gene in a consanguineous family with multiple severe congenital abnormalities characteristic of FA. RAD51C is a member of the RAD51-like gene family involved in homologous recombination-mediated DNA repair. The mutation results in loss of RAD51 focus formation in response to DNA damage and in increased cellular sensitivity to the DNA interstrand cross-linking agent mitomycin C and the topoisomerase-1 inhibitor camptothecin. Thus, biallelic germline mutations in a RAD51 paralog are associated with an FA-like syndrome.

The Lead Cancer Nurse - an ill-defined role?

The Lead Cancer Nurse (LCN) role was developed following the publication of the NHS Cancer Plan [Department of Health (2000) The NHS Cancer Plan. A Plan for Investment. A Plan for Reform. HMSO, London]. In collaboration with the Lead Cancer Clinician and Cancer Manager the role of the LCN is to contribute to the planning and delivery of cancer services in line with government guidance. However, there are significant variations in the remit and authority of the role between organizations, and limited research has been undertaken to evaluate the effectiveness of this senior nursing post. This article explores the complex and often ill-defined remit of the LCN role and compares this with Nurse Consultant and Advanced Nurse Practitioner roles. It explores the challenges that this presents both to the postholders and the organizations within which they work. Recommendations include on-going monitoring and evaluation of these posts, the development of local supportive frameworks and a review of the educational needs of these postholders.