Further evidence of contrasting phenotypes caused by reciprocal deletions and duplications: Duplication of nsd1 causes growth retardation and microcephaly

J. A. Rosenfeld, K. H. Kim, B. Angle, R. Troxell, J. L. Gorski, M. Westemeyer, M. Frydman, Y. Senturias, D. Earl, B. Torchia, R. A. Schultz, J. W. Ellison, K. Tsuchiya, S. Zimmerman, T. A. Smolarek, B. C. Ballif, L. G. Shaffer*

*Corresponding author for this work

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

Microduplications of the Sotos syndrome region containing NSD1 on 5q35 have recently been proposed to cause a syndrome of microcephaly, short stature and developmental delay. To further characterize this emerging syndrome, we report the clinical details of 12 individuals from 8 families found to have interstitial duplications involving NSD1, ranging in size from 370 kb to 3.7 Mb. All individuals are microcephalic, and height and childhood weight range from below average to severely restricted. Mild-to-moderate learning disabilities and/or developmental delay are present in all individuals, including carrier family members of probands; dysmorphic features and digital anomalies are present in a majority. Craniosynostosis is present in the individual with the largest duplication, though the duplication does not include MSX2, mutations of which can cause craniosynostosis, on 5q35.2. A comparison of the smallest duplication in our cohort that includes the entire NSD1 gene to the individual with the largest duplication that only partially overlaps NSD1 suggests that whole-gene duplication of NSD1 in and of itself may be sufficient to cause the abnormal growth parameters seen in these patients. NSD1 duplications may therefore be added to a growing list of copy number variations for which deletion and duplication of specific genes have contrasting effects on body development.

Original languageEnglish (US)
Pages (from-to)247-254
Number of pages8
JournalMolecular Syndromology
Volume3
Issue number6
DOIs
StatePublished - Jan 1 2013

Keywords

  • 5q35
  • Duplication
  • Growth retardation
  • Microcephaly
  • NSD1
  • Sotos syndrome
  • aCGH

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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    Rosenfeld, J. A., Kim, K. H., Angle, B., Troxell, R., Gorski, J. L., Westemeyer, M., Frydman, M., Senturias, Y., Earl, D., Torchia, B., Schultz, R. A., Ellison, J. W., Tsuchiya, K., Zimmerman, S., Smolarek, T. A., Ballif, B. C., & Shaffer, L. G. (2013). Further evidence of contrasting phenotypes caused by reciprocal deletions and duplications: Duplication of nsd1 causes growth retardation and microcephaly. Molecular Syndromology, 3(6), 247-254. https://doi.org/10.1159/00034557881264