Laurent Pasquier1, Mélanie Fradin2, Elouan Chérot3, Dominique Martin-Coignard4, Estelle Colin5, Hubert Journel6, Florence Demurger7, Linda Akloul8, Chloé Quélin9, Vincent Jauffret10, Josette Lucas11, Marc-Antoine Belaud-Rotureau12, Sylvie Odent13, Sylvie Jaillard14. 1. Service de Génétique Médicale, CHU Hôpital Sud, CLAD Ouest, Rennes, France. Electronic address: laurent.pasquier@chu-rennes.fr. 2. Service de Génétique Médicale, CHU Hôpital Sud, CLAD Ouest, Rennes, France. Electronic address: melanie.fradin@chu-rennes.fr. 3. Service de Génétique Médicale, CHU Hôpital Sud, CLAD Ouest, Rennes, France; Laboratoire de Cytogénétique et Biologie Cellulaire, CHU Pontchaillou, Rennes, France. Electronic address: elouan.cherot@chu-rennes.fr. 4. Service de Génétique, CH Le Mans, CLAD Ouest, Le Mans, France. Electronic address: dmartin@ch-lemans.fr. 5. Service de Génétique Médicale, CHU Angers, CLAD Ouest, Angers, France. Electronic address: escolin@chu-angers.fr. 6. Service de Génétique, CH Vannes, CLAD Ouest, Vannes, France. Electronic address: hubert.journel@ch-bretagne-atlantique.fr. 7. Service de Génétique Médicale, CHU Hôpital Sud, CLAD Ouest, Rennes, France. Electronic address: florence.demurger@chu-rennes.fr. 8. Service de Génétique Médicale, CHU Hôpital Sud, CLAD Ouest, Rennes, France. Electronic address: linda.akloul@chu-rennes.fr. 9. Service de Génétique Médicale, CHU Hôpital Sud, CLAD Ouest, Rennes, France. Electronic address: chloe.quelin@chu-rennes.fr. 10. Laboratoire de Cytogénétique et Biologie Cellulaire, CHU Pontchaillou, Rennes, France. Electronic address: vincent.jauffret@chu-rennes.fr. 11. Laboratoire de Cytogénétique et Biologie Cellulaire, CHU Pontchaillou, Rennes, France. Electronic address: josette.lucas@chu-rennes.fr. 12. Laboratoire de Cytogénétique et Biologie Cellulaire, CHU Pontchaillou, Rennes, France. Electronic address: marc-antoine.belaud-rotureau@chu-rennes.fr. 13. Service de Génétique Médicale, CHU Hôpital Sud, CLAD Ouest, Rennes, France; CNRS UMR 6290 (IGDR), Université de Rennes 1, France. Electronic address: sylvie.odent@chu-rennes.fr. 14. Laboratoire de Cytogénétique et Biologie Cellulaire, CHU Pontchaillou, Rennes, France; CNRS UMR 6290 (IGDR), Université de Rennes 1, France. Electronic address: sylvie.jaillard@chu-rennes.fr.
Abstract
BACKGROUND: While array-comparative genomic hybridization (a-CGH) and next-generation sequencing (NGS or exome) technologies have swiftly spread throughout the medical field, karyotype has gradually lost its leading role among genetic tests. Several international guidelines recommend starting with a-CGH screening then going on with exome analysis when investigating a patient with intellectual disability (ID) and no precise clinical diagnosis. A-CGH and whole exome sequencing increase etiologic diagnoses rate up to 30% in case of ID. However, physicians have to deal with the lack of qualitative information of the genome. Especially, exome and a-CGH analysis fail to detect chromosomal rearrangements because breakpoints are either located in introns or not associated with a gain or loss of genetic material. If these technologies cannot easily identify chromosomal translocations or inversions which sometimes split a gene, karyotype can. DISCUSSION: For the 5 cases described, karyotype provided the right diagnosis for a Mendelian disease while molecular analysis remained unsuccessful. We conclude that when a Mendelian disease is strongly suggested clinically, if molecular analysis is normal, it could be very useful to carry out a karyotype in order to demonstrate a chromosomal rearrangement involving the targeted gene. If this gene is disrupted, the physician can confirm the suspected disease and give appropriate genetic counseling. SUMMARY: This article aims at keeping in mind that karyotype, this old-fashioned genetic tool, can still remain powerful and useful within some genetic issues. Even in this modern period of whole exome sequencing, young geneticists should know that karyotype remains a powerful and cheap technology, available throughout the world and can still do a lot for families.
BACKGROUND: While array-comparative genomic hybridization (a-CGH) and next-generation sequencing (NGS or exome) technologies have swiftly spread throughout the medical field, karyotype has gradually lost its leading role among genetic tests. Several international guidelines recommend starting with a-CGH screening then going on with exome analysis when investigating a patient with intellectual disability (ID) and no precise clinical diagnosis. A-CGH and whole exome sequencing increase etiologic diagnoses rate up to 30% in case of ID. However, physicians have to deal with the lack of qualitative information of the genome. Especially, exome and a-CGH analysis fail to detect chromosomal rearrangements because breakpoints are either located in introns or not associated with a gain or loss of genetic material. If these technologies cannot easily identify chromosomal translocations or inversions which sometimes split a gene, karyotype can. DISCUSSION: For the 5 cases described, karyotype provided the right diagnosis for a Mendelian disease while molecular analysis remained unsuccessful. We conclude that when a Mendelian disease is strongly suggested clinically, if molecular analysis is normal, it could be very useful to carry out a karyotype in order to demonstrate a chromosomal rearrangement involving the targeted gene. If this gene is disrupted, the physician can confirm the suspected disease and give appropriate genetic counseling. SUMMARY: This article aims at keeping in mind that karyotype, this old-fashioned genetic tool, can still remain powerful and useful within some genetic issues. Even in this modern period of whole exome sequencing, young geneticists should know that karyotype remains a powerful and cheap technology, available throughout the world and can still do a lot for families.