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Phenotype–genotype correlation in a familial IGF1R microdeletion case
  1. D C M Veenma1,2,
  2. H J Eussen2,
  3. L C P Govaerts2,
  4. S W K de Kort1,
  5. R J Odink3,
  6. C H Wouters2,
  7. A C S Hokken-Koelega1,
  8. A de Klein2
  1. 1Department of Paediatrics, Erasmus MC, Rotterdam, the Netherlands
  2. 2Department of Clinical Genetics, Erasmus MC, Rotterdam, the Netherlands
  3. 3Department of Pediatrics, Catharina Hospital, Eindhoven, the Netherlands
  1. Correspondence to Dr A de Klein, Clinical Cytogeneticist, Department of Clinical Genetics, Erasmus MC Rm Ee 971, PO Box 2040, 3000 CA Rotterdam, the Netherlands; a.deklein{at}


Background IGF1R (insulin-like growth factor 1 receptor) haploinsufficiency is a rare event causing difficulties in defining clear genotype–phenotype correlations, although short stature is its well established hallmark. Several pure 15q26 monosomies (n=22) have been described in the literature, including those with breakpoints proximal to the IGF1R gene. Clinical heterogeneity is characteristic for these mainly de novo telomeric deletions and is illustrated by the involvement of several different organ systems such as the heart, diaphragm, lungs, kidneys and limbs, besides growth failure in the patient's phenotype. The clinical variability in these patients could be explained by the haploinsufficiency of multiple genes besides the IGF1R gene. In comparison, the six different IGF1R mutations revealed to date exhibit some variance in their clinical features as well, probably because different parts of the downstream IGF1R signalling cascade were affected.

Methods and results Using the recently developed technique multiplex ligation dependent probe amplification (MLPA), a chromosome 15q26.3 microdeletion harbouring part of the IGF1R gene was identified in a Dutch family. This deletion segregated with short height in seven out of 14 relatives across three generations. Metaphase fluorescence in situ hybridisation (FISH) and Affymetrix 250k single nucleotide polymorphism (SNP) microarray were used to characterise the deletion into more detail and showed that exons 11–21 of the IGF1R and a small hypothetical protein (LOC 145814) were deleted.

Conclusion Clinical work-up of this newly identified family, which constitutes the smallest (0.095 Mb) pure 15q26.3 interstitial deletion to date, confirms that disruption of the IGF1R gene does not induce major organ malformation or severe mental retardation.

  • IGF1R
  • 15q deletion
  • familial
  • growth retardation
  • endocrinology
  • clinical genetics
  • genetic screening/counselling

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  • Funding This research was funded in part by the Sophia Foundation for Scientific Research, Rotterdam, The Netherlands (SSWO project 551).

  • Competing interests None.

  • Patient consent Obtained.

  • Ethics approval This study was conducted with the approval of the Medical Ethical Test Commission, Erasmus MC, Rotterdam, The Netherlands (METC, Rotterdam).

  • Provenance and peer review Not commissioned; externally peer reviewed.