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

Meriam Hadj Amor,Sarra Dimassi,Wafa Slimani,Amel Taj,Adnene Mlika,Ali Saad,Khaled Ben Helel,Soumaya Mougou-Zerelli,Hanene Hannachi

doi:10.1186/s12881-020-0966-9

Abstract

BackgroundWhile 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.MethodsIn 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.ResultsA 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).Conclusions17p13.3 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.

Highlights

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
We report a familial translocation (3;17) leading to two different cytogenetic rearrangements resulting in a duplication/deletion of the 17p13.3 critical region for Miller-Dieker syndrome critical region (MDS) including PAFAH1B1 and tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein epsilon (YWHAE) genes and 3p26 region including contactin 4 (CNTN4), contactin 6 (CNTN6), CRBN and a part of close homolog of L1 (CHL1)
Fluorescent in situ hybridization (FISH) was first performed on the sister (II-7) using the subtelomeric probes (Vysis) of chromosome 17p and showed the absence of a subtelomeric signal on one of the chromosomes 17p (Fig. 3a)

Summary

Introduction

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. The diagnosis of human chromosome abnormalities including gain or loss of genomic copy numbers has extremely benefited from the development of advanced molecular cytogenetic methods such as array-CGH. This allows high-resolution pangenomic analysis, in particular in detecting genetic imbalances, defining their size, delimiting translocation breakpoints and analyzing the involved segments [1]. Array-CGH has identified novel co-locating micro-deletions and micro-duplication in the same locus. This has allowed the description of new. The duplication and deletion of the same chromosomal region resulted as expected in distinct phenotypic features in the offspring.

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