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Recurrent small deletions in KCNQ1OT1: a challenge for pathogenicity prediction
  1. Thomas Eggermann
  1. Institute of Human Genetics, Medical Faculty, RWTH Aachen, Aachen, Germany
  1. Correspondence to Professor Thomas Eggermann, Institute of Human Genetics, Aachen, Germany; teggermann{at}

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In the articles linked to this commentary and also published by the Journal of Medical Genetics, two groups independently report on the same small deletion in 11p15.5 which affects the imprinting centre 2 (IC2).1 2 With another recently published patient,3 now three families with the same rare molecular deletion of 132 bp in the IC2 are documented. In two families, the growth retardation phenotype segregates with the paternal origin of the affected allele and fits with the imprinting status of the region, but the description of a healthy carrier of the 132 bp deletion in the paternal IC2 copy by Stoltze2 shows that this conclusion has to be regarded with caution. Thus, the three cases confirm the complexity of CNVs affecting the imprinting centres in 11p15.5 and indicate that further, so far, unknown factors contribute to the clinical outcome of carriers of 11p15.5 alterations.

In this commentary, and in the three publications reviewed,1–3 the deletion is described as Chr11:2,720,964–2,721,095 in CGRCh37. This nomenclature is retained here, but the reader is advised that the Human Genome Variation Society (HGVS) suggested genomic reporting of the deletion is as follows: NC_000011.9:g.2720965_2721096del.

The IC2 is one of the two imprinting control regions in 11p15.5, disturbances in which are associated with two opposite growth disturbance phenotypes: Silver-Russell and Beckwith-Wiedemann syndrome (SRS, OMIM 180860; BWS, OMIM 130650). Different types of molecular alterations of both regions have been identified, comprising uniparental disomies (UPDs), CNVs, small base pair alterations (SNVs) in imprinted genes and imprinting defects (IDs, i.e., loss or gain of methylation, LoM, GoM). LoM of the IC1 is the major molecular defect in the growth retardation syndrome SRS, with up to 67.6% of molecularly …

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  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Provenance and peer review Commissioned; internally peer reviewed.

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