The Surprises of Molecular Testing in Neurofibromatosis Type 1: Rare Association between Two Mutational Variants Download PDF

Neurofibromatosis 1 (NF1 MIM # 162200) is one of the most prevalent illnesses that is inherited dominantly through autosomes. It is sometimes referred to as von Recklinghausen disease. The main features of this condition include neurocutaneous manifestations including café au lait spots, intertriginous freckling, different types of neurofibromas (cutaneous neurofibromas or plexiform tumors), neurological symptoms, and bone abnormalities. It happens at a rate of 1 in 3000 to 1 in 4000 occurrences. Cone-rod dystrophies are part of a diverse set of retinal dystrophies characterized by destruction to cone and rod cells, resulting in a wide range of clinical symptoms. Multiple genes contribute to the development of cone-rod dystrophy, with over 100 genes found so far. Among them is the CRX gene, which is linked to the autosomal dominant type of the condition. The authors describe a fascinating example of a patient diagnosed with Neurofibromatosis type 1 (NF1) as a baby, who developed myopia and astigmatism at age 15, leading to an unexpected outcome in molecular testing. A molecular DNA examination revealed the presence of two mutational variants: a pathogenic variant in the NF1 gene, c.3871-2A, and a possibly pathogenic variant in the CRX gene c.119G>A. The authors use this instance to demonstrate the unexpected findings from molecular testing in a disorder often diagnosed based on clinical criteria, offering patients expert genetic guidance.