Genotype-phenotype correlations for the type 1 lissencephaly of eight Tunisian children
Authors:   Department of Human Cytogenetics, Molecular Genetics and Reproductive Biology, Farhat Hached University Teaching Hospital, Sousse, Tunisia., Hadj Amor Meriam , Soyah Nejla ,   Pediatric department, Farhat Hached University Teaching Hospital, Sousse, Tunisia., Drouot Nathalie ,   Institute of Genetics and Molecular and Cellular Biology, Illkirch, France., Kraoua Ichraf ,   Department of Child and Adolescent Neurology, National Institute Mongi Ben Hmida of Neurology, Tunis, Tunisia., Khelifa Hela Ben ,   Department of Human Cytogenetics, Molecular Genetics and Reproductive Biology, Farhat Hached University Teaching Hospital, Sousse, Tunisia., Slimani Wafa ,   High Institute of Biotechnology, Monastir University, Monastir, Tunisia., Dimassi Sarra ,   Department of Human Cytogenetics, Molecular Genetics and Reproductive Biology, Farhat Hached University Teaching Hospital, Sousse, Tunisia., Hannachi Hanene ,   Department of Human Cytogenetics, Molecular Genetics and Reproductive Biology, Farhat Hached University Teaching Hospital, Sousse, Tunisia., Attig Ahlem ,   Department of Human Cytogenetics, Molecular Genetics and Reproductive Biology, Farhat Hached University Teaching Hospital, Sousse, Tunisia., Klai Hedia ,   Department of Child and Adolescent Neurology, National Institute Mongi Ben Hmida of Neurology, Tunis, Tunisia., Mlika Adnene ,   Pediatric department, Farhat Hached University Teaching Hospital, Sousse, Tunisia., Boughamoura Lamia ,   Pediatric department, Farhat Hached University Teaching Hospital, Sousse, Tunisia., Helel Khaled Ben ,   Pediatric department, Ibn Jazzar University Teaching Hospital, Kairouan, Tunisia, Turki Ilhem ,   Department of Child and Adolescent Neurology, National Institute Mongi Ben Hmida of Neurology, Tunis, Tunisia., Khouja Naziha Gouider ,   Department of Child and Adolescent Neurology, National Institute Mongi Ben Hmida of Neurology, Tunis, Tunisia., Chelly Jamel ,   Institute of Genetics and Molecular and Cellular Biology, Illkirch, France., Saad Ali ,   Common Service Units for Research in Genetics, Faculty of Medicine of Sousse, University of Sousse, Sousse, Tunisia., Zerelli Soumaya Mougou ,   Common Service Units for Research in Genetics, Faculty of Medicine of Sousse, University of Sousse, Sousse, Tunisia.
Published: May 2022

Background: Lissencephaly represents a rare subgroup of genetically distinct neurological disorders of neuronal migration characterized by a paucity or absence of cerebral gyration. The most common form of lissencephaly has been isolated and referred to as classic or type 1 lissencephaly. It is frequently related to abnormalities within LIS1 or DCX genes, with abnormalities ranging from single base pair substitutions to contiguous gene deletions. Methods: In this study, we report, for the first time, a clinical and genetic characterization of eight unrelated Tunisian children presenting type 1 lissencephaly. We screened LIS1 and DCX abnormalities thanks to a combination of molecular cytogenetic methods and next generation sequencing. Results: One deletion of DCX and three deletions of LIS1 were observed. One of these deletions was inherited from a maternal reciprocal translocation and estimated to approximately 2,9 Mb length. In addition, a 26 Kb LIS1 deletion was detected and refined between exon 3 up to exon 11 by target capture and sequencing. The last LIS1 rearrangement was a mutation (c.779T>A, p.V260E). Finally, two novel DCX mutations were found out (c.910G>C, p.G304R/c.436T>C, p.F146L). Conclusions: Our data confirm the individuality and originality of type 1 lissencephaly on both the phenotypic and the genetic levels. Furthermore, our data confirm again that LIS1 and DCX are the most genes associated with type 1 lissencephaly and spotlight the usefulness of developing approaches and methods for detecting a large number of known causative gene mutations.