Quantitative phenotypic and network analysis of 1q44 microdeletion for microcephaly.
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.
Division of Pediatric Neurology, University of Alberta, Edmonton, Alberta, Canada.
Nicholas
N
Raun
Division of Pediatric Neurology, University of Alberta, Edmonton, Alberta, Canada.
Janette
J
Mailo
Division of Pediatric Neurology, University of Alberta, Edmonton, Alberta, Canada.
Egidio
E
Spinelli
Division of Pediatric Neurology, University of Alberta, Edmonton, Alberta, Canada.
Xu
X
He
Division of Pediatric Neurology, University of Alberta, Edmonton, Alberta, Canada.
Sarah
S
McAvena
Division of Pediatric Neurology, University of Alberta, Edmonton, Alberta, Canada.
Logan
L
Brand
Division of Pediatric Neurology, University of Alberta, Edmonton, Alberta, Canada.
Julia
J
O'Sullivan
Division of Neurodevelopmental and Neuromotor Pediatrics, University of Alberta, Edmonton, Alberta, Canada.
John
J
Andersen
Division of Pediatric Neurology, University of Alberta, Edmonton, Alberta, Canada.
Lawrence
L
Richer
Division of Pediatric Neurology, University of Alberta, Edmonton, Alberta, Canada.
Richard
R
Tang-Wai
Division of Pediatric Neurology, University of Alberta, Edmonton, Alberta, Canada.|Neuroscience and Mental Health Institute, University of Alberta, Edmonton, Alberta, Canada.|Department of Medical Genetics, University of Alberta, Edmonton, Alberta, Canada.
Francois V
FV
Bolduc
D002648:Child; D002872:Chromosome Deletion; D002878:Chromosomes, Human, Pair 1 / Q000737:chemistry*; D019295:Computational Biology; D056915:DNA Copy Number Variations; D053263:Gene Regulatory Networks; D034722:Heterogeneous-Nuclear Ribonucleoprotein U / Q000235:genetics; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics; D006801:Humans; D008607:Intellectual Disability / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D016547:Kinesins / Q000235:genetics; D008297:Male; D008831:Microcephaly / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000235:genetics; D010641:Phenotype; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics*
C000621393:HNRNPU protein, human; D034722:Heterogeneous-Nuclear Ribonucleoprotein U; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D011495:Histone-Lysine N-Methyltransferase; C506278:SMYD3 protein, human; C491754:AKT3 protein, human; D051057:Proto-Oncogene Proteins c-akt; C583839:KIF26B protein, human; D016547:Kinesins
1q43 deletion; AKT3; HNRNPU; TP53; microcephaly