Characterisation of TSC1 promoter deletions in tuberous sclerosis complex patients |
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| Authors: | Ans M W van den Ouweland Peter Elfferich Bernard A Zonnenberg Willem F Arts Tjitske Kleefstra Mark D Nellist Jose M Millan Caroline Withagen-Hermans Anneke J A Maat-Kievit Dicky J J Halley |
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| Affiliation: | 1Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands;2Department of Internal Medicine, UMC Utrecht, Utrecht, The Netherlands;3Department of Neurology, Erasmus Medical Center, Rotterdam, The Netherlands;4Department of Clinical Genetics, UMC St Radboud, Nijmegen, The Netherlands;5Unit of Genetics, Hospital La Fe and CIBERER, Valencia, Spain |
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| Abstract: | Tuberous sclerosis complex (TSC), an autosomal dominant disorder, is a multisystem disease with manifestations in the central nervous system, kidneys, skin and/or heart. Most TSC patients carry a pathogenic mutation in either TSC1 or TSC2. All types of mutations, including large rearrangements, nonsense, missense and frameshift mutations, have been identified in both genes, although large rearrangements in TSC1 are scarce. In this study, we describe the identification and characterisation of eight large rearrangements in TSC1 using multiplex ligation-dependent probe amplification (MLPA) in a cohort of 327 patients, in whom no pathogenic mutation was identified after sequence analysis of both TSC1 and TSC2 and MLPA analysis of TSC2. In four families, deletions only affecting the non-coding exon 1 were identified. In one case, loss of TSC1 mRNA expression from the affected allele indicated that exon 1 deletions are inactivating mutations. Although the number of TSC patients with large rearrangements of TSC1 is small, these patients tend to have a somewhat milder phenotype compared with the group of patients with small TSC1 mutations. |
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| Keywords: | TSC1 promoter deletions MLPA |
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