Targeted Next Generation Sequencing reveals previously unidentified TSC1 and TSC2 mutations

BMC Medical Genetics

Wilfred FJ van IJcken²  Annelies de Klein³  Dicky Halley³  Ans van den Ouweland³  Anneke JA Maat-Kievit³  Floor E Jansen¹  Marie-Claire de Wit⁴  Anna E Koopmans⁵  Mike MP van den Berg⁵  Alan Mrsic³  Marianne Hoogeveen-Westerveld³  Lida Prins-Bakker³  Caroline Withagen-Hermans³  Monique van Veghel-Plandsoen³  Christel EM Kockx²  Rutger WW Brouwer²  Mark Nellist³ 

[1] Department of Pediatric Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, 3508, EA, The Netherlands;Center for Biomics, Erasmus Medical Center, Wytemaweg 80, Rotterdam, 3015, CN, The Netherlands;Department of Clinical Genetics, Ee-2426, Erasmus Medical Center, Wytemaweg 80, Rotterdam, 3015, CN, The Netherlands;Department of Neurology, Sophia Children’s Hospital, Erasmus Medical Center, Wytemaweg 80, Rotterdam, 3015, CN, The Netherlands;Department of Ophthalmology, Erasmus Medical Center, Wytemaweg 80, Rotterdam, 3015, CN, The Netherlands

关键词: Next Generation Sequencing;    HaloPlex;    TSC2;    TSC1;    Tuberous sclerosis complex;   

Others  :  1171808
DOI  :  10.1186/s12881-015-0155-4

 received in 2014-06-25, accepted in 2015-02-16,  发布年份 2015

【 摘 要 】

Background

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder caused by mutations in TSC1 and TSC2. Conventional DNA diagnostic screens identify a TSC1 or TSC2 mutation in 75 - 90% of individuals categorised with definite TSC. The remaining individuals either have a mutation that is undetectable using conventional methods, or possibly a mutation in another as yet unidentified gene.

Methods

Here we apply a targeted Next Generation Sequencing (NGS) approach to screen the complete TSC1 and TSC2 genomic loci in 7 individuals fulfilling the clinical diagnostic criteria for definite TSC in whom no TSC1 or TSC2 mutations were identified using conventional screening methods.

Results

We identified and confirmed pathogenic mutations in 3 individuals. In the remaining individuals we identified variants of uncertain clinical significance. The identified variants included mosaic changes, changes located deep in intronic sequences and changes affecting promoter regions that would not have been identified using exon-only based analyses.

Conclusions

Targeted NGS of the TSC1 and TSC2 loci is a suitable method to increase the yield of mutations identified in the TSC patient population.

【 授权许可】

   
2015 Nellist et al.; licensee BioMed Central.

【 图 表 】

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