INTRODUCTION: Germline heterozygous mutations in the tumor suppresser NF1 gene cause a cancer predisposition syndrome known as neurofibromatosis type 1 (NF1). This disease is one of the most common multisystem disorders with an estimated incidence of 1 in 3,000 to 1 in 4,000 births. Clinically, NF1 patients are prone to develop "café au lait" spots, neurofibromas, Lisch nodules, freckling of the axillary, or inguinal region and optic nerve gliomas. MATERIALS AND METHODS: In the present study, we report clinical and molecular findings of five unrelated patients and seven cases from four families with NF1 from UAE. To reveal the genetic defects underlying NF1 in our cohort of patients, we screened the whole coding and splice site regions of the NF1 gene. In addition, MLPA or CGH array has been used to screen for structural variations including deletions, indels, and complex rearrangements. RESULTS: This resulted in the identification of five distinct novel mutations and two previously reported ones. These variations included three missense and one nonsense mutations, one single base, one dinucleotide, and one large deletion. CONCLUSION: Four mutations were inherited, and the remaining were absent from both parents and therefore are "de novo" mutations. This analysis represents the spectrum of NF1 mutations in UAE and supports the premise of absence of hotspot mutations in the NF1 gene. Moreover, no obvious genotype-phenotype correlations were observed in our patients.
INTRODUCTION: Germline heterozygous mutations in the tumor suppresser NF1 gene cause a cancer predisposition syndrome known as neurofibromatosis type 1 (NF1). This disease is one of the most common multisystem disorders with an estimated incidence of 1 in 3,000 to 1 in 4,000 births. Clinically, NF1patients are prone to develop "café au lait" spots, neurofibromas, Lisch nodules, freckling of the axillary, or inguinal region and optic nerve gliomas. MATERIALS AND METHODS: In the present study, we report clinical and molecular findings of five unrelated patients and seven cases from four families with NF1 from UAE. To reveal the genetic defects underlying NF1 in our cohort of patients, we screened the whole coding and splice site regions of the NF1 gene. In addition, MLPA or CGH array has been used to screen for structural variations including deletions, indels, and complex rearrangements. RESULTS: This resulted in the identification of five distinct novel mutations and two previously reported ones. These variations included three missense and one nonsense mutations, one single base, one dinucleotide, and one large deletion. CONCLUSION: Four mutations were inherited, and the remaining were absent from both parents and therefore are "de novo" mutations. This analysis represents the spectrum of NF1 mutations in UAE and supports the premise of absence of hotspot mutations in the NF1 gene. Moreover, no obvious genotype-phenotype correlations were observed in our patients.
Authors: A C Jones; M M Shyamsundar; M W Thomas; J Maynard; S Idziaszczyk; S Tomkins; J R Sampson; J P Cheadle Journal: Am J Hum Genet Date: 1999-05 Impact factor: 11.025
Authors: D Barker; E Wright; K Nguyen; L Cannon; P Fain; D Goldgar; D T Bishop; J Carey; B Baty; J Kivlin Journal: Science Date: 1987-05-29 Impact factor: 47.728
Authors: T M Gray; E J Arnoys; S Blankespoor; T Born; R Jagar; R Everman; D Plowman; A Stair; D Zhang Journal: Protein Sci Date: 1996-04 Impact factor: 6.725
Authors: Bin Yin; Ruud Delwel; Peter J Valk; Margaret R Wallace; Mignon L Loh; Kevin M Shannon; David A Largaespada Journal: Blood Date: 2008-10-23 Impact factor: 22.113
Authors: Nahla N Abdel-Aziz; Ghada Y El-Kamah; Rabab A Khairat; Hanan R Mohamed; Yehia Z Gad; Akmal M El-Ghor; Khalda S Amr Journal: Mol Genet Genomic Med Date: 2021-06-03 Impact factor: 2.183