engleski

Towards a genotype-phenotype correlation of small supernumerary marker chromosomes (sSMC).

Introduction: Small supernumerary marker chromosomes (sSMC) are present in 0.043% of newborn. In about 30% of sSMC carriers an abnormal phenotype is observed. Clinical outcome of sSMC presence is difficult to predict as different phenotypic consequences can appear due to, differences in euchromatic DNA-content, uniparental disomy (UPD) of the sSMC’ s homologous chromosomes, and/or different degrees of mosaicism. Methods: We did own studies on >300 cases with sSMC using (sub)centromer-specific probe-sets ([sub]cenM-FISH ; Starke et al., 2003, Hum Genet 114:51-67) and array-CGH. Moreover, we performed a review of the literature (i.e. ~2000 cases with sSMC by 07/2006, see http://mti-n.mti.uni-jena.de/~huwww/MOL_ZYTO/sSMC.htm) Results: We suggest a first detailed and chromosome specific genotype/phenotype correlation for sSMC. I.e. small proximal trisomies of Xp, Xq, 1p/q, 2p, 4q, 5p, 6q, 7q, 8p/q, 12p/q, 14q, 17q, 18q, 19q, 20/20p lead to clinical manifestations, while small partial proximal trisomies of 2q, 5q, 7p, 15q, 17p, 18p, 21q, 22q may not be associated with significant clinical symptoms. No correlation could be found for mosaicism of sSMC and clinical symptoms. Recent own studies using (sub)cenM-FISH gave evidence that this may be in parts due to the fact, that different derivative-types of a sSMC are present which could not be detected and characterized before the development of subcenM-FISH. Conclusions: In summary, ~50 year after description of the first sSMC, molecular cytogenetics provides finally approaches for their comprehensive characterization. The new knowledge coming from that will lead to an improved genetic counseling of cases especially with de novo sSMC. Finally, it will be possible to define clear syndromes within the clinically and genetically group of ‘ patients with sSMC. Supported by the Dr. Robert Pfleger-Stiftung, DFG (436 RUS 17/135/03 ; 436 RUS 17/109/04, 436 WER 17/1/04, 436 WER 17/5/05, 436 RUS 17/22/06, WE 3617/2-1), DAAD, Schering Foundation, Boehringer Ingelheim Fonds, Ev. Studienwerk Villigst.

Small supernumerary marker chromosomes (sSMC); genotype-phenotype correlation; (sub)cenM-FISH; arrayCGH

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