Journal article
2q24 Deletions: Further Characterization of Clinical Findings and Their Relation to the SCN Cluster
American journal of medical genetics. Part A, Vol.158(11), pp.2767-2774
2012
DOI: 10.1002/ajmg.a.35362
PMID: 23023937
Abstract
As the resolution of molecular cytogenetic methods continues to improve, it has become increasingly possible to refine genotype–phenotype correlations based upon gene involvement. We report three new patients with nonrecurrent deletions involving subbands of 2q24. These patients were referred for evaluation of developmental delay, but were found to have unique, nonoverlapping clinical features. Patient 1 presented with infantile seizures, microcephaly, and brain anomalies, along with facial dysmorphism, growth retardation, neuromuscular scoliosis, and later with developmental regression. Array comparative genomic hybridization (aCGH) detected an 8 Mb interstitial deletion encompassing the neuronal sodium channel (SCN) gene cluster. Patient 2 presented with growth retardation, congenital heart defect, and hypotonia. Patient 3 presented with developmental delay and behavioral problems. Patients 2 and 3 had no history of seizures, microcephaly, or brain anomalies and were found to have deletions of 2q24, ∼8 Mb and <500 kb respectively, centromeric to and outside the SCN cluster. It has been demonstrated that mutations and copy number variants (CNVs) affecting the SCN gene cluster result in severe, early-onset seizures. It is however, less clear whether haploinsufficiency of regions outside the SCN cluster may result in phenotypically recognizable and clinically significant features. We discuss additional dosage sensitive genes that may exist outside the SCN cluster. Our and published data indicate that 2q24 deletions not involving the SCN cluster are associated with fewer neurobehavioral problems, but may predispose to congenital malformations.
Details
- Title: Subtitle
- 2q24 Deletions: Further Characterization of Clinical Findings and Their Relation to the SCN Cluster
- Creators
- Manjunath NIMMAKAYALU - Division of Medical Genetics, Department of Pediatrics, University of Iowa Hospitals and Clinics, Iowa City, Iowa, United StatesNathan NOBBLE - Division of Medical Genetics, Department of Pediatrics, University of Iowa Hospitals and Clinics, Iowa City, Iowa, United StatesV Kim Horton - Division of Medical Genetics, Department of Pediatrics, University of Iowa Hospitals and Clinics, Iowa City, Iowa, United StatesMarcia WILLING - Department of Pediatrics, Washington University School of Medicine, St Louis, Missouri, United StatesSara COPELAND - Genetic Services Branch, Division of Services for Children with Special Health Needs, Maternal and Child Health Bureau, Rockville, Maryland, United StatesVal SHEFFIELD - Division of Medical Genetics, Department of Pediatrics, University of Iowa Hospitals and Clinics, Iowa City, Iowa, United StatesPeter L NAGY - Department of Pathology and Cell Biology, Columbia University Medical Center, New York, New York, United StatesTom WASSINK - Division of Medical Genetics, Department of Pediatrics, University of Iowa Hospitals and Clinics, Iowa City, Iowa, United StatesShivanand PATIL - Division of Medical Genetics, Department of Pediatrics, University of Iowa Hospitals and Clinics, Iowa City, Iowa, United StatesOleg A SHCHELOCHKOV - Division of Medical Genetics, Department of Pediatrics, University of Iowa Hospitals and Clinics, Iowa City, Iowa, United States
- Resource Type
- Journal article
- Publication Details
- American journal of medical genetics. Part A, Vol.158(11), pp.2767-2774
- Publisher
- Wiley-Liss; Chichester
- DOI
- 10.1002/ajmg.a.35362
- PMID
- 23023937
- ISSN
- 1552-4825
- eISSN
- 1552-4833
- Language
- English
- Date published
- 2012
- Academic Unit
- Psychiatry; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Medical Genetics and Genomics; Ophthalmology and Visual Sciences
- Record Identifier
- 9984065489302771
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