Two independent variants causing neurofibromatosis type 1 in one Chinese family

Abstract

Objective: Neurofibromatosis type 1, resulting from NF1 mutation, is estimated to affect one in 3000 people worldwide. NF1 is a pathogenic gene with one of the highest mutation rates in humans. This study was aimed to report a case in which members of a Chinese family had two distinct NF1 variants. Methods: DNA was isolated from the peripheral blood of the proband and his wife and affected son. Whole-exome sequencing was performed on the proband, while next-generation sequencing was used to detect NF1 and other related genes in his wife and son. Sanger sequencing was conducted to confirm the variants. Results: An unreported variant c.6143T>G and a recurrent variant c.1063-2A>G of NF1 were identified in the proband and his affected son, respectively. The latter variant was not found in the peripheral blood lymphocytes of the proband and his wife. Paternity testing confirmed their parent-child relationship. We summarized the findings of similar reported cases. Conclusion: Our study described a rare phenomenon in which one Chinese family had independent NF1 variants. The findings indicate that clinicians need to sequence the whole NF1 gene of all family members rather than merely verifying the suspect variant detected in the proband.