Quantitative phenotypic and network analysis of 1q44 microdeletion for microcephaly

Am J Med Genet A. 2017 Apr;173(4):972-977. doi: 10.1002/ajmg.a.38139.


As genome wide techniques become more common, an increasing proportion of patients with intellectual disability (ID) are found to have genetic defects allowing genotype-phenotype correlations. Previously, AKT3 deletion was suggested to be responsible for microcephaly in patients with 1q43-q44 deletion syndrome, but this does not correspond to all cases. We report a case of a de novo 1q44 deletion in an 8-year-old boy with microcephaly in whom AKT3 is not deleted. We used a systematic review of the literature, our patient, and network analysis to gain a better understanding of the genetic basis of microcephaly in 1q deletion patients. Our analysis showed that while AKT3 deletion is associated with more severe (≤3 SD) microcephaly in 1q43-q44 deletion patients, other genes may contribute to microcephaly in AKT3 intact patients with microcephaly and 1q43-44 deletion syndrome. We identified a potential role for HNRNPU, SMYD3, NLRP3, and KIF26B in microcephaly. Overall, our study highlights the need for network analysis and quantitative measures reporting in the phenotypic analysis of a complex genetic syndrome related to copy number variation.

Keywords: 1q43 deletion; AKT3; HNRNPU; TP53; microcephaly.

Publication types

  • Case Reports

MeSH terms

  • Child
  • Chromosome Deletion*
  • Chromosomes, Human, Pair 1 / chemistry*
  • Computational Biology
  • DNA Copy Number Variations
  • Gene Regulatory Networks*
  • Heterogeneous-Nuclear Ribonucleoprotein U / genetics
  • Histone-Lysine N-Methyltransferase / genetics
  • Humans
  • Intellectual Disability / diagnosis
  • Intellectual Disability / genetics*
  • Intellectual Disability / pathology
  • Kinesins / genetics
  • Male
  • Microcephaly / diagnosis
  • Microcephaly / genetics*
  • Microcephaly / pathology
  • NLR Family, Pyrin Domain-Containing 3 Protein / genetics
  • Phenotype
  • Proto-Oncogene Proteins c-akt / genetics*


  • HNRNPU protein, human
  • Heterogeneous-Nuclear Ribonucleoprotein U
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • NLRP3 protein, human
  • Histone-Lysine N-Methyltransferase
  • SMYD3 protein, human
  • AKT3 protein, human
  • Proto-Oncogene Proteins c-akt
  • KIF26B protein, human
  • Kinesins