A novel multion in a Chinese family with neurofibromatosis type 1: A case report

Neurofibromatosis type 1 (NF1), an autosomal dominant genetic disorder, exhibits a high prevalence across populations. The quintessential clinical manifestations of NF1 encompass a spectrum of features, including neurofibromas, café-au-lait macules (CALMs), skinfold freckling, Lisch nodules, and an array of central nervous system tumors. The pathogenesis of NF1 is intricately tied to mutations within the NF1 gene, situated on chromosome 17q11.2. This gene encodes the neurofibromin protein, whose functional loss leads to deregulated cell growth, thereby fostering an environment conducive to tumorigenesis.

A 23-year-old female developed freckles under her armpits more than a decade ago. CALMs and hypertrophic papules appeared on her trunk and extremities. Their size and quantity gradually increased, with the largest lesion reaching 3.1 cm. There were no specific discomforts such as itching or pain.Her sister and mother have the same manifestations.

The proband has more than 6 CALMs and more than 2 neurofibromas visible all over the body, with scattered freckles in the axillae. Similar rashes are also observed in his/her mother and younger sister. Therefore, the patient is diagnosed with NF1.

As the proband has a need for pregnancy, we performed Sanger sequencing on the genes of the proband and their family members.

A novel mutation located in the NF1 gene was identified, and genetic counseling was provided to the proband.

This study unveiled a novel pathogenic nonsense mutation, designated as NF1 c.240_243del (p.Q83*), within the proband's genetic sequence. This mutation introduces a premature stop codon, resulting in the truncation of the neurofibromin protein. This truncation, in turn, precipitates the onset of NF1, underscoring the critical role of the NF1 gene in maintaining normal cellular growth and proliferation.