Neurofibromatosis Type I

Disease Overview Von Recklinghausen’s disease, also called Neurofibromatosis Type I (NF1) is one of the most common types of inherited single gene disorder which effects approximately 1 in a disorder caused by a mutation in the tumor suppressor neurofibromin (NF1) gene located on chromosome 17 q11.2 and is inherited in an autosomal dominant manner. The neurofibromin gene primarily affects the development and growth of neural cell tissues as well as the regulation of melanogenesis so the defect in this gene typically causes neural cell tissue masts, pigment changes. Neurofibromatosis 1 can also cause a multitude of other disorders such as cognitive disorders, skeletal and vascular dysplasia’s, the exact genotype-phenotype correlation is unknown
The individuals who would need molecular testing would be: 1individuals who are suspected as having NF1 but do not fulfill the NIH diagnostic criteria (mainly young children); 2 in young children with a serious tumor where n NF1 diagnosis would affect management; 3 in an adult if prenatal or preimplantation genetic diagnosis in a pregnancy (current or future) is likely to occur; 4 in some families with spinal Neurofibromatosis 1 or the NF1 affected individuals do not meet the NIH diagnostic criteria, in which case molecular testing is used for diagnosis of at risk relatives in families who do not meet the NIH criteria for diagnosis of Neurofibromatosis 1 (Friedman 2014). There are several molecular genetic tests for NF1: Comprehensive multistep mutation detection, Genomic DNA sequence analysis, Deletion/ duplication analysis, and Cytogenetic analysis. The comprehensive multistep mutation detection protocol has been effective in detecting 95% of individuals with a pathogenic NF1 variant while Genomic sequencing, deletion/duplication analysis, and Cytogenetic analysis have only been able to detect a defect in the NF1 gene in 61%, 5%, and less than 1% of individuals. The most effective method of detection, the comprehensive multi-step screening approach analyses both mRNA, genomic DNA, and tests for whole NF1 deletions (Friedman 2014). The testing begins with an optimized protein truncation test, then a fluorescent in situ hybridization analysis, followed by direct sequencing, a long range reverse transcriptase PCR with Southern blot analysis and, if necessary, cytogenetic analysis although it is only used in a select few laboratories (Boyd et al. 2009). Although genetic testing is successful in determining whether an individual has Neurofibromatosis type 1, the test is unable to determine the severity or outcome of the