title: Maternal complex chromosomal rearrangement leads to TCF12 microdeletion in a patient presenting with coronal craniosynostosis and intellectual disability.
abstract: We report on a young child with intellectual disability and unilateral coronal craniosynostosis leading to craniofacial malformations. Standard karyotype showed an apparently balanced translocation between chromosomes 2 and 15 [t(2;15)(q21;q21.3)], inherited from his mother. Interestingly, array-CGH 180K showed a 3.64 Mb de novo deletion on chromosome 15 in the region 15q21.3q22.2, close to the chromosome 15 translocation breakpoints. This deletion leads to haploinsufficiency of TCF12 gene that can explain the coronal craniosynostosis described in the patient. Additional FISH analyses showed a complex balanced maternal chromosomal rearrangement combining the reciprocal translocation t(2;15)(q21;q21.3), and an insertion of the 15q22.1 segment into the telomeric region of the translocated 15q fragment. The genomic imbalance in the patient is likely caused by a crossing-over that occurs in the recombination loop formed during the maternal meiosis resulting in the deletion of the inserted fragment. This original case of a genomic microdeletion of TCF12 exemplifies the importance of array-CGH in the clinical investigation of apparently balanced rearrangements but also the importance of FISH analysis to identify the chromosomal mechanism causing the genomic imbalance.
authors.affiliation: Laboratoire de Génétique Chromosomique, Département de Génétique et Procréation, Hôpital Couple Enfant, CHU Grenoble, Grenoble, France.
authors.forename: Pauline
authors.initials: P
authors.lastname: Le Tanno
authors.forename: Brice
authors.initials: B
authors.lastname: Poreau
authors.forename: Francoise
authors.initials: F
authors.lastname: Devillard
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Vieville
authors.forename: Florence
authors.initials: F
authors.lastname: Amblard
authors.forename: Pierre-Simon
authors.initials: PS
authors.lastname: Jouk
authors.forename: Véronique
authors.initials: V
authors.lastname: Satre
authors.forename: Charles
authors.initials: C
authors.lastname: Coutton
mesh_terms: D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics*; D002675:Child, Preschool; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D055028:Comparative Genomic Hybridization; D003398:Craniosynostoses / Q000235:genetics*; D019066:Facies; D017353:Gene Deletion; D057895:Haploinsufficiency; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008607:Intellectual Disability / Q000235:genetics*; D059785:Karyotype; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D014178:Translocation, Genetic
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; C073366:TCF12 protein, human
keywords: 15q21 deletion; TCF12; array-CGH; complex chromosomal rearrangement; craniosynostosis; insertion; intellectual disability; translocation