Neuronal migration genes and a familial translocation t (3;17): candidate genes implicated in the phenotype

BMC Med Genet. 2020 Feb 6;21(1):26. doi: 10.1186/s12881-020-0966-9.


Background: While Miller-Dieker syndrome critical region deletions are well known delineated anomalies, submicroscopic duplications in this region have recently emerged as a new distinctive syndrome. So far, only few cases have been described overlapping 17p13.3 duplications.

Methods: In this study, we report on clinical and cytogenetic characterization of two new cases involving 17p13.3 and 3p26 chromosomal regions in two sisters with familial history of lissencephaly. Fluorescent In Situ Hybridization and array Comparative Genomic Hybridization were performed.

Results: A deletion including the critical region of the Miller-Dieker syndrome of at least 2,9 Mb and a duplication of at least 3,6 Mb on the short arm of chromosome 3 were highlighted in one case. The opposite rearrangements, 17p13.3 duplication and 3p deletion, were observed in the second case. This double chromosomal aberration is the result of an adjacent 1:1 meiotic segregation of a maternal reciprocal translocation t(3,17)(p26.2;p13.3).

Conclusions: 17p13.3 and 3p26 deletions have a clear range of phenotypic features while duplications still have an uncertain clinical significance. However, we could suggest that regardless of the type of the rearrangement, the gene dosage and interactions of CNTN4, CNTN6 and CHL1 in the 3p26 and PAFAH1B1, YWHAE in 17p13.3 could result in different clinical spectrums.

Keywords: CHL1; Miller-Dieker syndrome critical region; PAFAH1B1; Partial monosomy 3p26.2; Partial trisomy 17p13.3.

Publication types

  • Case Reports

MeSH terms

  • 1-Alkyl-2-acetylglycerophosphocholine Esterase / genetics
  • 14-3-3 Proteins / genetics
  • Cell Adhesion Molecules / genetics
  • Cell Movement / genetics
  • Child, Preschool
  • Chromosome Deletion
  • Chromosomes, Human, Pair 17 / genetics
  • Chromosomes, Human, Pair 3 / genetics
  • Classical Lissencephalies and Subcortical Band Heterotopias / diagnosis
  • Classical Lissencephalies and Subcortical Band Heterotopias / genetics*
  • Classical Lissencephalies and Subcortical Band Heterotopias / physiopathology
  • Comparative Genomic Hybridization
  • Contactins / genetics
  • Female
  • Gene Dosage / genetics
  • Genetic Association Studies
  • Humans
  • In Situ Hybridization, Fluorescence
  • Lissencephaly / diagnosis
  • Lissencephaly / genetics*
  • Lissencephaly / physiopathology
  • Meiosis / genetics
  • Microtubule-Associated Proteins / genetics
  • Neurons / metabolism
  • Neurons / pathology*
  • Phenotype
  • Translocation, Genetic / genetics*
  • Trisomy / genetics


  • 14-3-3 Proteins
  • CHL1 protein, human
  • CNTN4 protein, human
  • CNTN6 protein, human
  • Cell Adhesion Molecules
  • Contactins
  • Microtubule-Associated Proteins
  • YWHAE protein, human
  • 1-Alkyl-2-acetylglycerophosphocholine Esterase
  • PAFAH1B1 protein, human

Supplementary concepts

  • Chromosome 17, trisomy 17p
  • Chromosome 3, monosomy 3p