Abstract：High-throughput sequencing was performed for the peripheral blood DNA from two probands in the family with tuberous sclerosis complex (TSC) to determine the sequences of TSC-related genes TSC1 and TSC2 and their splicing regions and identify mutation sites. Amplification primers were designed for the mutation sites and polymerase chain reaction and Sanger sequencing were used to verify the sequences of peripheral blood DNA from the probands and their parents. The two probands had c.3981-3982 insA (p.Asp1327AspfsX87) and c.4013-4014 delCA (p.Ser1338Cysfs) heterozygous mutations, respectively, in the TSC2 gene. The parents of proband 1 had no abnormalities at these two loci; the mother of proband 2 had c.4013-4014 delCA heterozygous mutation in the TSC2 gene, while the father and the grandparents of proband 2 had no abnormalities. c.3981-3982 insA mutation may cause early coding termination of amino acid sequence at the 1413th site, and c.4013-4014 delCA mutation may cause early coding termination of amino acid sequence at the 1412th site. These two mutations are the pathogenic mutations for families 1 and 2, respectively, and both of them are novel frameshift mutations, but their association with the disease needs to be further verified by mutant protein function cell model and animal model.
Huang CH, Peng SS, Weng WC, et al. The relationship of neuroimaging findings and neuropsychiatric comorbidities in children with tuberous sclerosis complex[J]. J Formos Med Assoc, 2015, 114(9):849-854.
[2]
Ismail NF, Nik Abdul Malik NM, Mohseni J, et al. Two novel gross deletions of TSC2 in Malaysian patients with tuberous sclerosis complex and TSC2/PKD1 contiguous deletion syndrome[J]. Jpn J Clin Oncol, 2014, 44(5):506-511.
Kozlowski P, Roberts P, Dabora S, et al. Identification of 54 large deletions/duplications in TSC1 and TSC2 using MLPA, and genotype-phenotype correlations[J]. Hum Genet, 2007, 121(3-4):389-400.
[5]
De Waele L, Lagae L, Mekahli D. Tuberous sclerosis complex:the past and the future[J]. Pediatr Nephrol, 2015, 30(10):1771-1780.
[6]
Mazhab-Jafari MT, Marshall CB, Ho J, et al. Structure-guided mutation of the conserved G3-box glycine in Rheb generates a constitutively activated regulator of mammalian target of rapamycin (mTOR)[J]. J Biol Chem, 2014, 289(18):12195-12201.
[7]
Astrinidis A, Henske EP. Tuberous sclerosis complex:linking growth and energy signaling pathways with human disease[J]. Oncogene, 2005, 24(50):7475-7481.
[8]
Mayer K. Characterisation of a novel TSC2 missense mutation in the GAP related domain associated with minimal clinical manifestations of tuberous sclerosis[J]. J Med Genet, 2004, 41(5):e64.
[9]
Chen CP, Su YN, Hung CC, et al. Novel mutation in the TSC2 gene associated with prenatally diagnosed cardiac rhabdomyomas and cerebral tuberous sclerosis[J]. J Formos Med Assoc, 2006, 105(7):599-603.
[10]
Yu Z, Zhang X, Guo H, et al. A novel TSC2 mutation in a Chinese family with tuberous sclerosis complex[J]. J Genet, 2014, 93(1):169-172.
[11]
Curatolo P, Moavero R, Roberto D, et al. Genotype/phenotype correlations in tuberous sclerosis complex[J]. Semin Pediatr Neurol, 2015, 22(4):259-273.
[12]
Liu L, Pan Y, Song Y, et al. Activation of AMPK α2 inhibits airway smooth muscle cells proliferation[J]. Eur J Pharmacol, 2016, 791:235-243.
