Whole-exome sequencing revealed a novel heterozygous variant of NF1 in a Vietnamese family with neurofibromatosis type I

Abstract Background Neurofibromatosis type I (NF1) is one of the most common autosomal dominant disorders caused by mutations in the NF1 gene. Pathogenic variants in this gene induce a wide range of phenotypes, including dermal neurofibromas along nerves, skinfold frecklings, iris hamartomas, skeletal deformity, and mental health problems. Malignancy, the most prevalent and serious complication of NF1 significantly reduces the life quality of patients. This study investigated the molecular etiology underlying neurofibromatosis type I in a Vietnamese family with two affected members. Result A novel variant NM_000267.3: c.2034del, p.Ile679Phefs*9 in the NF1 gene was detected in the two patients by whole-exome sequencing (WES). This variant was validated as the causative variant by Sanger sequencing. Conclusion This is the first study in a Vietnamese family to report a novel NF1 variant, increasing the mutation breadth and underscoring the importance of integrating clinical and molecular insights to diagnose genetic diseases that present a wide spectrum of phenotypical expression. Regular follow-ups by a team of specialists, including oncologists, should be considered as part of the management plan for this condition.