Array reportNarrowing the critical region for overgrowth within 13q14.2-q14.3 microdeletions
Introduction
Tosca et al. described a patient with a 13q13.3q21.3 microdeletion and a patient with a 13q14.2q21.2 microdeletion who had overgrowth and dysmorphic features (Tosca et al., 2011). We describe two additional patients with smaller chromosomal microdeletions and this adds to the previously reported phenotypes and may refine the critical region of genes related to increased growth.
Section snippets
Clinical report
Patient 1 was referred to clinical genetics services because of developmental delay, tall stature and a previous diagnosis of Sotos syndrome made by his paediatrician. He is the first child of healthy unrelated parents. There is no family history of intellectual disability or large stature and the mid-parental height was 180 cm (75th centile). He was delivered at full term following an uncomplicated pregnancy with a birth weight of 3.74 kg (50th centile), length of 57 cm (2 cm > 97th centile),
Materials and methods
A 60K ISCA oligonucleotide comparative genomic hybridization (CGH) array (BlueGnome, Cambridge, UK), analysed with BlueMulti v2.6 software was performed on DNA from patient 1. Patient 2's DNA was analysed using a 44K oligonucleotide comparative genomic hybridization (CGH) array (Agilent Technologies, Walldbronn, Germany).
Metaphase FISH studies using the RP11-384G23 probe (TCAG, Toronto Canada) were performed for confirmation of the deletion in patient 1 and his parents. Metaphase FISH studies
Results
Patient 1 had a 4.61 Mb deletion encompassing 21 protein coding genes (chr13: 50604180-55215160, hg19). Patient 2 had a 4.13 Mb deletion encompassing 34 protein coding genes (chr13:49569993-53703546, hg 19) (Fig. 2). FISH analysis showed the deletions arose de novo and there was no evidence of parental translocations. Therefore, the minimum critical hypothesised overgrowth region is chr13:50604180-53703546, hg19. This 3.10 Mb region contains 21 protein coding genes (Fig. 2).
Discussion
There is an important overlap between tumour suppressor genes and overgrowth. Whilst deleting tumour suppressor genes may lead to cancer in somatic tissues, an overgrowth phenotype may occur if a deletion occurs in the germline and this is exemplified by an increased risk of neoplasia within overgrowth syndromes (Lapunzina, 2005).
The DECIPHER database lists 17 patients with overlapping deletions, although 14 of the overlapping deletions are very large. Two patients (DECIPHER IDs 266015 and
Online resources
DECIPHER (URL: http://decipher.sanger.ac.uk/) [April 2015].
UCSC Genome Browser (URL: https://genome.ucsc.edu/index.html) [June 2015].
Pubmed (URL: http://www.ncbi.nlm.nih.gov/pubmed/) [August 2015].
The Jackson Laboratory (URL: https://www.jax.org/#) [August 2015].
International Mouse Phenotyping Consortium (URL: http://www.mousephenotype.org) [August 2015].
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