Characterisation of TSC1 promoter deletions in Tuberous Sclerosis Complex patients

Ans van den Ouweland (1) , Peter Elfferich (1) , Bernard Zonnenberg (1) , Tjitske Kleefstra (1) , Mark Nellist (1) , José M Millán (1) , Caroline Withagen-Hermans (1) , Anneke Maat-Kievit (1) , D.J.J. Halley (1) , Willem F. Arts (1)

1 Department of Clinical Genetics

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. Here we describe the identification and characterisation of 8 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 4 families, deletions only affecting the noncoding 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, one gets the impression that these patients have a somewhat milder phenotype compared to the group of patients with small TSC1 mutations.

Mots clés: TSC1; promoter; MLPA deletions

Ans van den Ouweland, Peter Elfferich, Bernard Zonnenberg, Tjitske Kleefstra, Mark Nellist, et al.. Characterisation of TSC1 promoter deletions in Tuberous Sclerosis Complex patients. European Journal of Human Genetics, 2010, ⟨10.1038/ejhg.2010.156⟩. ⟨hal-00580683⟩