Neurofibromatosis Type 1 Individuals Research Articles

Evaluation of primary haemostasis in people with neurofibromatosis type 1.

Assessment of haemostasis in people with neurofibromatosis type 1 (NF-1) is essentially lacking, despite case reports of an association with von Willebrand disorder (VWD) and reported excessive bleeding post-surgery. We assessed routine blood haematology, routine coagulation parameters [prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT) and fibrinogen], coagulation factors II, V, VII, VIII, IX, X, XI and XII, von Willebrand (VWF) factor antigen and activity, and platelet function [using the platelet function analyser (PFA-100)] in a group of individuals with NF-1 (n = 30). Their perceived haemorrhagic bleeding risk was also graded by means of a structured clinical assessment and physical examination. Routine blood assessments including platelet counts were generally normal, as were the routine coagulation tests PT, TT and fibrinogen, and most coagulation factors. Elevated APTTs were detected in 11 individuals, reduced factor XII levels in three, reduced VWF levels in four, and elevated PFA closure times (CTs) in 13. Laboratory results correlated with each other in some but not all cases. For example, elevated APTTs were identified in two of three individuals with a reduced factor XII level and prolonged CTs were identified in three individuals who also showed reduced aggregation responses in classical platelet function studies. Moreover, all individuals with VWF results below the normal reference range showed elevated CTs with both PFA test cartridges, and those with VWF results identified as borderline normal (i.e. 50-65%) also showed elevated CTs with both PFA test cartridges in three of five cases. The relationship between VWF and CTs was also identified by linear regression analysis (P-values of <0.05, for all comparisons). However, as clinically perceived bleeding risk did not appear to be correlated with laboratory test results in most cases, blanket screening of NF-1 individuals for evaluation of laboratory haemostasis may not be warranted.

Characterization of six mutations in exon 37 of neurofibromatosis type 1 gene.

Neurofibromatosis type 1 (NF1) is one of the most common inherited disorders, with an incidence of 1 in 3,000. We screened a total of 320 unrelated NF1 patients for mutations in exon 37 of the NF1 gene. Six independent mutations were identified, of which three are novel, and these include a recurrent nonsense mutation identified in 2 unrelated patients at codon 2281 (G2281X), a 1-bp insertion (6791 ins A) resulting in a change of TAG (tyrosine) to a TAA (stop codon), and a 3-bp deletion (6839 del TAC) which generated a frameshift. Another recurrent nonsense mutation, Y2264X, which was detected in 2 unrelated patients in this study, was also previously reported in 2 NF1 individuals. All the mutations were identified within a contiguous 49-bp sequence. Further studies are warranted to support the notion that this region of the gene contains highly mutable sequences.