Craniofacial Characteristics of NF1 Determined by Genetic Analysis
Objectives: Neurofibromatosis type 1 (NF1) is a common autosomal dominant disorder that affects 1/3500 individuals. 80% of NF1 is caused by NF1 germline mutations. It has been reported that 5% of NF1 patients carry a deletion of 1.5 Mb involving the NF1 gene. The aim of this study was to clarify the difference of the oral characteristics between types of NF1 germline mutations and NF1 deletions. Methods: Four patients were diagnosed NF1 gene deletion using by FISH analysis with the BAC clone, and the range of the deficiency of the gene was detected. Three of the patients who did not show any deficiency by FISH were tried to detect any mutation point site using PCR-direct sequence method. Orofacial and dental characteristics were evaluated using by panoramic and lateral cephalometric radiographs, and dental cast including the palatal form, occlusion, tooth form and size, and dental arch form.
Results: The range of the deficiency in four subjects was found as 1.5Mb by analyzed with FISH. PCR-analyzing direct sequences for three patients without any deletion showed that nonsense mutation (c.574C > T (p.Arg192X)), the splice mutation (c.1185 + 1G > A) and missense mutation (c.5207T > G (p.Val1736Gly)). Oral abnormalities including primary fused teeth and congenitally missing permanent teeth were observed in 2 patients within only microdeletion type (microdeletion type 2/4 and mutation type 0/3). Prevalence of tooth deformities was significantly higher in microdeletion type than mutation type. Conclusion: Not only variable facial dysmorphism, mental retardation, developmental delay, cardiovascular deformity, and diffuse neurofibromas but also oral abnormalities were severely affected in microdeletion type compared with mutation type of NF1.
Division: IADR/PER General Session
Meeting:2010 IADR/PER General Session (Barcelona, Spain) Location: Barcelona, Spain
Year: 2010 Final Presentation ID:4429 Abstract Category|Abstract Category(s):Craniofacial Biology
Authors
Kobayashi, Ryosuke
( Nihon University School of Dentistry at Matsudo, Matsudo,Chiba, N/A, Japan
)
Takahashi, Yasuo
( Division of Pediatric Dentistry, Saitama Children's Medical Center, Saitama, N/A, Japan
)
Shimizu, Kenji
( Division of Medical Genetics, Saitama Children's Medical Center, Saitama, N/A, Japan
)
Ohashi, Hirofumi
( Division of Medical Genetics, Saitama Children's Medical Center, Saitama, N/A, Japan
)
Maeda, Takahide
( Nihon University School of Dentistry at Matsudo, Matsudo,Chiba, N/A, Japan
)
Hirai, Norimitsu
( Nihon University School of Dentistry at Matsudo, Matsudo,Chiba, N/A, Japan
)
Takahashi, Masai
( Nihon University School of Dentistry at Matsudo, Matsudo,Chiba, N/A, Japan
)
Orino, Daisuke
( Nihon University School of Dentistry at Matsudo, Matsudo,Chiba, N/A, Japan
)
Koba, Kazue
( Division of Pediatric Dentistry, Saitama Children's Medical Center, Saitama, N/A, Japan
)
Mitsui, Norimasa
( Division of Medical Genetics, Saitama Children's Medical Center, Saitama, N/A, Japan
)
Watanabe, Shigehiko
( Division of Medical Genetics, Saitama Children's Medical Center, Saitama, N/A, Japan
)
Suzuki, Atsushi
( Division of Medical Genetics, Saitama Children's Medical Center, Saitama, N/A, Japan
)
Matsune, Kensuke
( Nihon University School of Dentistry at Matsudo, Matsudo,Chiba, N/A, Japan
)
SESSION INFORMATION
Poster Session
Craniofacial Development
07/17/2010