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A de novo 2.78-Mb duplication on chromosome 21q22.11 implicates candidate genes in the partial trisomy 21 phenotype
- Source :
- NPJ Genomic Medicine
- Publication Year :
- 2017
- Publisher :
- Nature Publishing Group, 2017.
-
Abstract
- Down syndrome (DS) is the most common genetic cause of intellectual disability (ID) and in the majority of cases is the result of complete trisomy 21. The hypothesis that the characteristic DS clinical features are due to a single DS critical region (DSCR) at distal chromosome 21q has been refuted by recently reported segmental trisomy 21 cases characterised by microarray-based comparative genomic hybridisation (aCGH). These rare cases have implicated multiple regions on chromosome 21 in the aetiology of distinct features of DS; however, the map of chromosome 21 copy-number aberrations and their associated phenotypes remains incompletely defined. We report a child with ID who was deemed very high risk for DS on antenatal screening (1 in 13) and has partial, but distinct, dysmorphologic features of DS without congenital heart disease (CHD). Oligonucleotide aCGH testing of the proband detected a previously unreported de novo 2.78-Mb duplication on chromosome 21q22.11 that includes 16 genes; however, this aberration does not harbour any of the historical DSCR genes (APP, DSCR1, DYRK1A and DSCAM). This informative case implicates previously under-recognised candidate genes (SOD1, SYNJ1 and ITSN1) in the pathogenesis of specific DS clinical features and supports a critical region for CHD located more distal on chromosome 21q. In addition, this unique case illustrates how the increasing resolution of microarray and high-throughput sequencing technologies can continue to reveal new biology and enhance understanding of widely studied genetic diseases that were originally described over 50 years ago.
- Subjects :
- 0301 basic medicine
Genetics
Proband
Candidate gene
Down syndrome
0303 health sciences
Chromosome
Case Report
Biology
medicine.disease
DSCAM
03 medical and health sciences
030104 developmental biology
0302 clinical medicine
030220 oncology & carcinogenesis
Gene duplication
medicine
Erratum
Trisomy
Chromosome 21
Molecular Biology
030217 neurology & neurosurgery
Genetics (clinical)
030304 developmental biology
Subjects
Details
- Language :
- English
- ISSN :
- 20567944
- Volume :
- 2
- Database :
- OpenAIRE
- Journal :
- NPJ Genomic Medicine
- Accession number :
- edsair.doi.dedup.....0d10c1c6a8dc1e1d2b98e64456f642af