Neurofibromatosis type 1 families with first-degree relatives harbouring distinct pathogenic variants. Genetic counselling and familial diagnosis: what should be offered?

Unlabelled: Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder caused by pathogenic variants in Recently, testing has been included as a clinical criterion for NF1 diagnosis. Additionally, preconception genetic counselling in patients with NF1 focuses on a 50% risk of transmitting the familial variant as the risk of having a sporadic NF1 is considered the same as the general population.

Methods: 829 individuals, 583 NF1 sporadic cases and 246 patients with NF1 with documented family history, underwent genetic testing for NF1.

A highly sensitive genetic protocol to detect NF1 mutations.

Neurofibromatosis type 1 (NF1) is a hereditary disorder caused by mutations in the NF1 gene. Detecting mutation in NF1 is hindered by the gene's large size, the lack of mutation hotspots, the presence of pseudogenes, and the wide variety of possible lesions. We developed a method for detecting germline mutations by combining an original RNA-based cDNA-PCR mutation detection method and denaturing high-performance liquid chromatography (DHPLC) with multiplex ligation-dependent probe amplification (MLPA).