Diagnostic exome sequencing identifies a heterozygous MBD5 frameshift mutation in a family with intellectual disability and epilepsy |
| |
| Affiliation: | 1. Department of Pediatrics, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea;2. Department of Laboratory Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea;3. Catholic Genetic Laboratory Center, Seoul St. Mary''s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea;4. Department of Laboratory Medicine, Green Gross Genome, Yongin, Republic of Korea;1. Institute of Medical Genetics, Tokyo Women''s Medical University, Tokyo, Japan;2. Department of Medical Genetics, Osaka Women''s and Children''s Hospital, Osaka, Japan;3. School of Medicine and Public Health, Faculty of Health and Medicine, University of Newcastle, Callaghan, NSW, Australia;1. INSERM, U 1127, ICM, F-75013 Paris, France;2. CNRS, UMR 7225, ICM, F-75013 Paris, France;3. Sorbonne Universités, UPMC Univ Paris 06, UMR S 1127, F-75013 Paris, France;4. Institut du Cerveau et de la Moelle épinière, ICM, F-75013 Paris, France;1. Division of Pediatric Neurology, Department of Pediatrics, Duke Children’s Hospital and Health Center, Suite T0913J, 2301 Erwin Road, Durham, NC 27710, USA;2. Center of Human Genome Variation, LSRC, Duke University School of Medicine, 201 Trent Drive, Durham, NC 27710, USA;1. Department of Neuropediatrics, Centre de Reference des Epilepsies Rares, Hopital Necker Enfants Malades, Paris Descartes University, Paris, France;2. Inserm U663, University Paris Descartes, PRES Sorbonne Paris Cité, Paris F-75005; CEA, Neurospin, 91190 Gif/Yvette, France;3. Department of Genetics, Inserm U781, Hopital Necker Enfants Malades, Paris Descartes University, Paris, France;4. APHM, CINAPSE, Pediatric Neurology Department, Timone Children Hospital, Marseille, France;5. Department of Pediatric Neurology, Hôpital Erasme, Bruxelles, Belgium;6. Department of Pediatric Radiology, Hopital Necker Enfants Malades, APHP, Paris, Descartes University, Paris, France;1. Laboratory of Molecular Medicine and Genomics, Department of Medicine and Surgery, University of Salerno, Baronissi, Italy;2. Fondazione IRCCS SDN, 80143 Napoli, Italy;3. Child and Adolescent Neuropsychiatry, Department of Medicine and Surgery and “SS. Giovanni di Dio e Ruggi d’Aragona – Schola Medica Salernitana” Hospital of the University of Salerno, Salerno, Italy;4. Pediatric Neurology and Clinical Neurophysiology Unit, Department of Pediatrics, University of Padova, Italy;5. Deparment of Pediatrics DPMSC, University of Udine, Udine, Italy;6. Child and Adolescent Neuropsychiatry, Department of Pediatrics, University of Turin, Turin, Italy;7. Department of Pediatrics, University of Chieti, Chieti, Italy;8. Molecular Pathology and Medical Genomics, “SS. Giovanni di Dio e Ruggi d’Aragona – Schola Medica Salernitana” Hospital of the University of Salerno, Salerno, Italy |
| |
| Abstract: | ![]()
Methyl-CpG-binding domain 5 (MBD5)-associated neurodevelopmental disorder caused by 2q23.1 or MBD5-specific mutation has been recently identified as a genetic disorder associated with autism spectrum disorders. Phenotypic features of 2q23.1 deletion or disruption of MBD5 gene include severe intellectual disability, seizure, significant speech impairment, sleep disturbance, and autistic-like behavioural problems. Here we report a 7-year-old girl with intellectual disability and epilepsy without previous clinical diagnosis. Diagnostic exome sequencing identified a novel frameshift mutation c.254_255delGA (p.Arg85Asnfs*6) in the MBD5 gene of the proband and her father. The proband's father with normal intelligence showed subclinical manifestations observed in subsequent investigations. Clinical manifestations, disease course, and molecular findings of the involvement of MBD5 gene in this family suggest an unusual MBD5-related neurodevelopmental disorder. Moreover, this report demonstrates the critical role of next-generation sequencing technique in characterizing such a rare disorder with variable or no clinical manifestation and providing opportunity to develop effective preventive measures such as pre-implantation genetic diagnosis. |
| |
| Keywords: | diagnostic exome sequencing Frameshift mutation Intellectual disability Epilepsy |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
