Mutational Analysis of the NF1 Gene in Two Families with Neurofibromatosis 1 Accompanied by Pheochromocytoma.
10.3803/EnM.2011.26.2.177
- Author:
Hyon Seung YI
1
;
Sei Hyun KIM
;
Jihoon KIM
;
Eun Jin BAE
;
Suntaek HONG
;
Ie Byung PARK
;
Yu Jin KIM
;
Sihoon LEE
Author Information
1. Department of Internal Medicine and Laboratory of Molecular Endocrinology, Gachon University School of Medicine, Incheon, Korea. shleemd@gachon.ac.kr
- Publication Type:Case Report
- Keywords:
Neurofibromatosis type 1;
NF1 gene;
Pheochromocytoma
- MeSH:
Adult;
DNA;
Exons;
Female;
Genes, Neurofibromatosis 1;
Genes, Tumor Suppressor;
Genotype;
Germ-Line Mutation;
GTPase-Activating Proteins;
Humans;
Male;
Middle Aged;
Nervous System;
Neurofibromatoses;
Neurofibromatosis 1;
Neurofibromin 1;
Phenotype;
Pheochromocytoma;
RNA, Messenger;
Siblings
- From:Endocrinology and Metabolism
2011;26(2):177-184
- CountryRepublic of Korea
- Language:English
-
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.
