Autor(es):
Pinto da Costa, Eurico 
; Oliveira, Jorge ; Silva, João ; Santos, Rosário
Data: 2012
Identificador Persistente: http://hdl.handle.net/10400.18/934
Origem: Repositório Científico do Instituto Nacional de Saúde
Assunto(s): CDLS; NIPBL; SMC1A; HRM; Doenças Genéticas
Descrição
Resumo publicado em: European Journal of Human Genetics. 2012 Jun 1;20 Suppl 1: Sec1:298 Cornelia de Lange Syndrome [CdLS (MIM#122470)] is a rare multisystemic disorder, characterized by a
typical phenotype that includes distinctive facial dysmorphism, hirsutism, growth and psychomotor
developmental delay, abnormalities of the upper extremities, and relatively frequent gastrointestinal and
congenital heart defects. CdLS is essentially caused by mutations in the NIPBL and SMC1A genes (~50%
and 5% of cases, respectively), but mutations have been also described in other genes (PDS5A, PDS5B,
SMC3) (http://www.lovd.nl/CDLS). This genetic heterogeneity in CdLS can however be explained by a close
functional relationship at the cellular level, since all these proteins are involved in chromatid cohesion.
The molecular and clinical characterization of 42 Portuguese CdLS patients has been previously described
(Oliveira et al., 2010). In this work we conducted the molecular analysis of NIPBL gene and more recently
expanded this study to other 20 patients. Subsequently, all the molecularly unresolved patients were
screened for large deletions and duplications in NIPBL by MLPA, and point mutations in SMC1A by high
resolution melting curve analysis and sequencing.
Preliminary results allowed us to identify 4 previously known mutations (including a case with somatic
mosaicism), 3 novel mutations (c.3316C>T, c.6983C>G and c.7307C>T) and 2 large deletions in the NIPBL
gene. Mutation screening in SMC1A is still ongoing.
Our results, at least for NIPBL gene analysis, suggest that the use of several different techniques is essential
for attaining a high mutation detection rate. CdLS cases with somatic mosaicism are probably
underestimated in the literature and may explain some degree of phenotypical variability.
