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- array-CGH, microarray based comparative genomic hybridisation
- FISH, fluorescent in situ hybridisation
- GTG, G-bands by trypsin using Giemsa
- RHG, R-bands by heat using Giemsa
- TAR, telomere associated repeat
Chromosomal anomalies account for a substantial proportion of syndromes associated with mental retardation. Some of these anomalies result in a specific phenotype which may direct the clinician towards the diagnosis.1,2 Deletion of the most distal band on the short arm of chromosome 1 (1p36) is the most common terminal deletion syndrome, affecting 1 out of 5000 newborns. It results in a clinically recognisable syndrome characterised by a specific facial gestalt including large anterior fontanel, deep-set eyes, flat nasal bridge, asymmetric ears, and pointed chin.3,4 Additional clinical features include learning disability, seizure, cardiomyopathy, and hearing impairment.
Detailed molecular characterisation of patients with 1p36 constitutional deletions showed variability in the parental origin, deletion size, and complexity of the chromosomal rearrangements, as well as in the clinical presentation of the syndrome.3 These observations led Wu et al to propose that “haploinsufficiency of contiguous, but functionally unrelated, genes in the deletion region are responsible for the phenotypic features”. Therefore, they postulated that “refining the sizes of the deletions in affected individuals, in conjunction with phenotype/genotype correlation, will aid in identifying candidate genes within critical deletion intervals”.5
Indeed, genotype/phenotype correlations allowed the assignment of certain clinical features to specific deletion intervals. In particular, the critical region associated with hearing loss was refined5 and some candidate genes associated with epilepsy phenotype6 and clefting abnormalities were identified.7
More recently, microarray based comparative genomic hybridisation (array-CGH) was applied to DNA from patients with 1p36 constitutional deletions.8 Results showed the accuracy of array-CGH for detection of single DNA copy number changes and fine mapping of imbalance breakpoints.
In this study, we applied array-CGH to six patients showing clinical features characteristic of monosomy 1p36 with a microarray composed of 2221 overlapping clones covering 99.5% of the euchromatic portion of chromosome …
This work was funded by the Wellcome Trust and by INSERM. Richard Redon was supported by a Sanger Institute Postdoctoral Fellowship.
Competing interests: none declared