Mutational Analysis of the NF1 Gene in Two Families with Neurofibromatosis 1 Accompanied by Pheochromocytoma
Endocrinology and Metabolism
;
: 177-184, 2011.
Article
Dans Anglais
| WPRIM
| ID: wpr-121309
ABSTRACT
Neurofibromatosis type 1 (NF1) is one of the most common autosomal dominant inherited disorders affecting the nervous system. NF1 is associated with mutations in the NF1 gene, which is located on chromosome sub-band 17q11.2 and contains 57 exons spanning approximately 300 kb of genomic DNA. NF1 is caused by a loss of function mutation of the NF1 gene, a tumor suppressor gene, which encodes for neurofibromin, a GTPase-activating protein (GAP) involved in the negative regulation of Ras activity. The GAP-related domain, which is encoded for by exons 20-27a, is one of the most important functional domains in neurofibromin. The cysteine-serine-rich domain has been recognized as an important functional domain in NF1-related pheochromocytomas. As the result of many genetic analyses of NF1-related pheochromocytomas, pheochromocytoma has generally been recognized as a true component of NF1. We recently experienced two families with NF1 accompanied by pheochromocytoma. The proband of family 1 is a 31-year-old female diagnosed with NF1 and pheochromocytoma. Gene analysis of the proband and her sister showed that the mutation of the NF1 gene (c.7907+1G>A) led to the skipping of exon 53 during NF1 mRNA splicing. The proband of family 2 is a 48-year-old male who was diagnosed with the same condition. Gene analysis demonstrated the mutation of the NF1 gene (c.5206-8C>G) with missplicing of exon 37. These novel germline mutations did not fall into the GAP-related nor the cysteine-serine-rich domains, but into the C-terminal area of the NF1 gene. This suggests that the correlation between the genotype and phenotype of NF1-related pheochromocytoma is somewhat difficult to characterize. Further studies will be necessary to confirm the function of the C-terminal area of the NF1 gene and its contribution to the development of NF1 and pheochromocytoma.
Texte intégral:
Disponible
Indice:
WPRIM (Pacifique occidental)
Sujet Principal:
Phénotype
/
Phéochromocytome
/
ADN
/
ARN messager
/
Exons
/
Gènes suppresseurs de tumeur
/
Gènes nf1
/
Neurofibromatose de type 1
/
Neurofibromatoses
/
Mutation germinale
Limites du sujet:
Adulte
/
Femelle
/
Humains
/
Mâle
langue:
Anglais
Texte intégral:
Endocrinology and Metabolism
Année:
2011
Type:
Article
Documents relatifs à ce sujet
MEDLINE
...
LILACS
LIS