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De novo 5q35.5 duplication with clinical presentation of Sotos syndrome
Author(s) -
Kasnauskiene Jurate,
Cimbalistiene Loreta,
Ciuladaite Zivile,
Preiksaitiene Egle,
Kučinskienė Zita Aušrelė,
Hettinger Joe A.,
Sismani Carolina,
Patsalis Philippos C.,
Kučinskas Vaidutis
Publication year - 2011
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.34179
Subject(s) - sotos syndrome , gene duplication , macrocephaly , biology , context (archaeology) , genetics , copy number variation , gene , phenotype , genome , paleontology
We report on a girl with developmental delay and a de novo 264 kb interstitial duplication in the region of Sotos syndrome at 5q35.3 in the immediate vicinity of critical NSD1 gene, but manifesting the phenotype, of overgrowth both prenatal stage and postnatal, macrocephaly, developmental delay, and resembling that of Sotos syndrome, rather than the recently reported syndrome of reciprocal duplication. The duplication is located right downstream from the NSD1 gene, a region which appears critical for the expression of the gene as regulatory elements might be disrupted or the expression of a not amplified critical gene might be otherwise affected by the duplicated region. Thus, in the process of evaluating identified CNVs attention should be drawn to the possible influence of chromosomal rearrangement on distant genes, which could add additional diversity to genomic disorders. Our case demonstrates that evaluation of the size of chromosomal alteration and gene content are not sufficient for assessment of CNV's pathogenicity and the context of adjacent genes should be considered. © 2011 Wiley‐Liss, Inc.