RESUMO
OBJECTIVE@#To report on a rare case of Neurofibromatosis type 2 (NF2) manifesting as oculomotor nerve palsy and explore its genetic basis.@*METHODS@#A patient with NF2 who had presented at Beijing Ditan Hospital Affiliated to Capital Medical University on July 10, 2021 was selected as the study subject. Cranial and spinal cord magnetic resonance imaging (MRI) was carried out on the patient and his parents. Peripheral blood samples were collected and subjected to whole exome sequencing. Candidate variant was verified by Sanger sequencing.@*RESULTS@#MRI revealed bilateral vestibular Schwannomas, bilateral cavernous sinus meningiomas, popliteal neurogenic tumors, and multiple subcutaneous nodules in the patient. DNA sequencing revealed that he has harbored a de novo nonsense variant of the NF2 gene, namely c.757A>T, which has replaced a codon (AAG) encoding lysine (K) at position 253 with a stop codon (TAG). This has resulted in removal of the Merlin protein encoded by the NF2 gene from position 253 onwards. The variant was not found in public databases. Bioinformatic analysis suggested that the corresponding amino acid is highly conserved. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was rated as pathogenic (PVS1+PS2+PM2_Supporting+PP3+PP4).@*CONCLUSION@#The heterozygous nonsense variant c.757A>T (p.K253*) of the NF2 gene probably underlay the disease in this patient with an early onset, atypical but severe phenotype.
Assuntos
Masculino , Humanos , Neurofibromatose 2/genética , Genes da Neurofibromatose 2 , Doenças do Nervo Oculomotor/genética , Biologia Computacional , Genômica , MutaçãoRESUMO
Atualmente neurofibromatose faz parte de um grupo de doenças heterogêneas. A neurofibromatose NF-1 é a mais comum das facomatoses ocorrendo em aproximadamente 90 por cento dos casos. A anomalia anastomótica mais comum entre as áreas supridas pela artéria carótida e a artéria vertebral é uma artéria de grosso calibre que se localiza ao nível do seio cavernoso. Esta comunicaçäo vascular na opiniäo de muitos pesquisadores é a primitiva artéria trigeminal. É apresentada uma paciente com neurofibromatose tipo NF-1 periférico que apresentou uma cefaléia explosiva seguida de agitaçäo psicomotora. A punçäo lombar revelou-se hemorrágica e o estudo angiográfico revelou um aneurisma de artéria carótida interna direita e uma larga comunicaçäo entre os sistemas carótido-basilar ao nível do seio cavernoso
Assuntos
Humanos , Feminino , Adulto , Artéria Carótida Interna/anormalidades , Artéria Carótida Interna , Genes da Neurofibromatose 1/genética , Genes da Neurofibromatose 2/genética , Cefaleia/etiologia , Aneurisma Intracraniano/genética , Neurofibromatose 1/genética , Neurofibromatose 2/genética , Seio CavernosoRESUMO
Cytogenetic analysis of 4 cases of meningiomas from 3 male and 1 female patients is reported. One of male patients suffered from neurofibromatosis type 2. Histologically, the meningiomas were meningotheliomatous (1), transitional (2), and psammomatous (1). Chromosomal abnormalities were found in all cases with a karyotype 45,XY,-22, 45,XY,-16, 45,XX,-2, and 45,XY,t (15p;22q), respectively. Monosomy of chromosome 22 was detected only in the patient with neurofibromatosis type 2. These cytogenetic analysis demonstrates that variable clonal karyotype aberrations exist in meningiomas.