A novel variant of NF1 gene in a patient with neurofibromatosis type 1: a case report

Neurofibromatosis type 1 in a patient with a unique c.1369_1370insGGGTC mutation in the NF1 gene

Neurofibromatosis type 1 (NF1) is a severe monogenic disorder characterized by café-au-lait spots and neoplastic lesions, including plexiform neurofibromas that are treated with targeted therapy using a mitogen-activated protein kinase inhibitor. A sporadic case of NF1 caused by a unique, previously unreported NF1 gene mutation, c.1369_1370insGGGTC(p.H457fs), was identified in a 13-year-old boy. The features of NF1 in the patient included early manifestation of tumor syndrome with simultaneous development of cutaneous neurofibromas, tumors of spinal roots, vagus nerve and plexiform neurofibromas, cognitive and speech impairment, growth retardation, and multiple skeletal abnormalities. At the age of 10, targeted therapy was initiated, resulting in a significant tumor size reduction and thus indicating the effectiveness of this approach in NF1 caused by this pathogenic NF1 variant.

Case Report: Clinical and molecular genetic analysis of a patient with coexisting complete androgen insensitivity syndrome and neurofibromatosis type 1 and 15pstk + polymorphism

This is the first report of concurrent CAIS and NF1, which enriches and expands the genotypic and phenotypic spectra of both disorders.

A case of neurofibromatosis type 1 caused by a novel NF1 mutation

Neurofibromatosis type 1 is an autosomal dominant disorder caused by loss-of-function mutations in the NF1 gene, leading to constitutive Ras pathway activation. NF1 gene mutations exhibit complete penetrance, cause high phenotypic variability, and feature diverse types without established hotspots. This study identified a novel pathogenic variant via whole-exome sequencing in a pediatric case, broadening the spectrum of known NF1 mutations. We further describe the clinical response to the MEK inhibitor selumetinib, including regression of subcutaneous nodules, with no significant improvement in cutaneous neurofibroma scores was observed.

Phenotypic and genotypic characteristics of pediatric patients with neurofibromatosis type 1: a 12-year single-center cohort study.

Clinical characteristics and variant spectrum of NF1 in Chinese patients with neurofibromatosis type 1: a cross-sectional study

Neurofibromatosis type 1 (NF1) is a rare autosomal dominant multisystem disorder caused by NF1 gene variants. Although NF1 shows marked clinical and genetic heterogeneity, large Chinese cohorts integrating clinical features, NF1 variant spectrum, and external variant contextualization remain limited. We conducted a cross-sectional study of 847 clinically confirmed Chinese patients with NF1 to characterize demographic features, clinical manifestations, DNB-defined severity, and NF1 variant spectrum. Whole-exome sequencing was performed in 211 patients. Transcript-level variant distribution was assessed using a 500-bp sliding-window approach and further contextualized using ClinVar-derived NF1 variant data. Among 847 patients, the median age was 23 years, 27.5% had a family history of NF1, and more than 90% were younger than 40 years. Café-au-lait macules, neurofibromas, and plexiform neurofibromas were observed in 98.3%, 70.7%, and 20.9% of patients, respectively. Younger age, lower neurofibroma burden, and absence of learning difficulties were associated with DNB-defined mild classification. Among 211 genetically tested patients, pathogenic/likely pathogenic NF1 variants were identified in 182 patients, 11 carried NF1 variants of uncertain significance, and 18 had no reportable NF1 variant. In total, 152 distinct NF1 variants were identified, including 45 novel sites. Transcript-level analysis showed regional variation in reportable nucleotide-level NF1 variants, with relatively higher variant density around exons 10–15 and 44–49. Comparison with ClinVar pathogenic/likely pathogenic NF1 variants showed no significant window-level difference after multiple-testing correction. This cross-sectional study summarizes the clinical and genetic features of Chinese patients with NF1 and expands the known NF1 variant spectrum in this population. Transcript-level analysis showed regional variation in reportable NF1 variants, broadly paralleling the ClinVar pathogenic/likely pathogenic NF1 variant distribution. These findings provide a basis for future longitudinal studies to validate clinically meaningful genotype–phenotype relationships in NF1.

A familial case of Noonan syndrome with multiple lentigines caused by a PTPN11 gene mutation: a case report

Introduction . The differential diagnosis of hypertrophic cardiomyopathy (HCM) requires the ruling out phenocopies. Noonan syndrome with multiple lentigines (NSML) is a rare genetic disorder with an autosomal dominant inheritance pattern, classified as a RASopathies. In 85% of cases, NSML is caused by mutations in the PTPN11 gene, which encodes the key enzyme in the RAS pathway, protein tyrosine phosphatase SHP2. The remaining cases are associated with mutations in the RAF1 and BRAF genes. Like other RASopathies, NSML presents with a phenotypic triad of facial dysmorphism, cardiopathy, and growth retardation. Distinctive features of NSML include cutaneous manifestations in the form of lentigines (90%) and a high (up to 80%) incidence of HCM phenocopy. Brief description . We described a familial case of NSML caused by the Thr468Met mutation in the PTPN11 gene. The proband was a 38-year-old woman with a long-term history of HCM. Facial dysmorphism was mild, and multiple lentigines were not associated with the disease. Left ventricular hypertrophy was concentric, with a maximum myocardial thickness of 34,5 mm. The disease course was complicated by presyncope due to ventricular tachycardia episodes. All of the patient’s children inherited NSML, had a typical facial phenotype, lentigo, and a phenocopy of HCM. In addition to HCM phenocopy, the patient’s eldest son and youngest daughter had pulmonary artery stenosis of varying severity. Discussion . Diagnosis of NSML in the proband was difficult due to a decrease in the severity of external signs with age and poor awareness among cardiologists of the external syndrome manifestations. This case demonstrates the variability of cardiac pathology within families and the importance of family screening and monitoring of family members for the timely diagnosis of cardiac pathology.