Data di Pubblicazione:
2009
Citazione:
Novel mutations in the CDKL5 gene, predicted effects and associated phenotypes / S. Russo, M. Marchi, F. Cogliati, M.T. Bonati, M. Pintaudi, E. Veneselli, V. Saletti, M. Balestrini, B. Ben Zeev, L. Larizza. - In: NEUROGENETICS. - ISSN 1364-6745. - 10:3(2009 Feb 25), pp. 241-250. [10.1007/s10048-009-0177-1]
Abstract:
It has been found that CDKL5 gene mutations are responsible for early-onset epilepsy and drug resistance. We screened a population of 92 patients with classic/atypical Rett syndrome, 17 Angelman/Angelman-like patients and six
idiopathic autistic patients for CDKL5 mutations and exon deletions and
identified seven novel mutations: six in the Rett subset and one in an Angelman
patient. This last, an insertion in exon 11, c.903_904 dupGA, p.Leu302Aspfx49X,
is associated with a relatively mild clinical presentation as the patient is the only one capable of sitting and walking alone. Of the six mutations, two are de novo missense changes affecting highly conserved aminoacid residues, c.215 T > C p.Ile72Thr and c.380A > G p.His127Arg (present in a mosaic condition) found in
two girls with the most severe clinical presentation, while the remaining are the
splicing c.145 + 2 T > C and c.2376 + 5G > A, the c.1648C > T p.Arg550X and the
MPLA-identified c.162_99del261 mutation. RNA characterisation of four mutations
revealed the aberrant transcript of the missense allele (case 2) and not the stop mutation (case 3), but also allowed the splicing mutation (case 1) and the
c.-162_99del261 (case 4) to be ategorised as truncating. The obtained data reinforce the view that a more severe phenotype is due more to an altered protein than haploinsufficiency. Furthermore, the mutational repertoire of the CDKL5 gene
is shown to be expanded by testing patients with phenotypical overlap to Rett syndrome and applying multiplex ligation-dependent probe amplification.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
Genotype-phenotype correlation; Mutation screening; RNA analysis
Elenco autori:
S. Russo, M. Marchi, F. Cogliati, M.T. Bonati, M. Pintaudi, E. Veneselli, V. Saletti, M. Balestrini, B. Ben Zeev, L. Larizza
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