PMC4131807_01
Details of growth - BMI-for age and facial/physical appearance of the patient. A. On the left, growth curves for our patient showing early-onset obesity; on the right, BMI at 41 and 53 months. The source of growth and BMI-for-age graphic is: http://www.chartsgraphsdiagrams.com/HealthCharts/growth-2-20-girls.html. B. Photographs of the patient: (a) frontal face, (b) lateral face, and (c) full frontal views. Note the square-shaped truncal build.
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The child developed obesity during early infancy, despite normal food-seeking behaviour (Additional file 1: Table S1.) and on our first examination at the age of 41 months her weight was 32 Kg (BMI = 23.59) (Figure 1A), length 128 cm ( > >97thc), OFC 51 cm (50-75thc). At last evaluation, at the age of 4 y and 4 mo, her growth parameters were: weight 39 kg (> > 97thc), length 128 cm (> > 97thc), OFC 51 cm (50-75thc), BMI 24.18 (Figure 1A). Facial examination showed slightly upturned nose and short neck without other remarkable dimorphisms (Figure 1B). The first symptom observed in our patient was very early-onset obesity (Figure 1A), starting from the 3rd month of life (Additional file 1: Table S1).
Molecular details of 2p25.3 deletion.Array- CGH profile of chromosome 2 showing (A) a terminal deletion of 1.9 Mb at 2p25.3, and (B) an enlargement of the 2p25.3 deletion. Genomic view of the terminal 1.9 Mb of chromosome 2p25.3(C): UCSC genes (GRCh37/hg19) are shown. The screenshot shows the deletion breakpoint disrupting MYT1L.
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Agilent Human Genome CGH Microarray Kit 180 k (Agilent Technologies Inc., Santa Clara, CA) with a resolution of ~40 Kb revealed a deletion of 1.9 Mb in chromosomal band 2p25.3 (Figure 2A) including the following genes : FAM110C (OMIM *611395) ACP1 (OMIM *171500), TMEM18 (OMIM *613200), SNTG2 (OMIM *608715), TPO (OMIM *608715), MYT1L (OMIM *613084) PXDN (OMIM *605158) and SH3YL1, FAM150B (Figure 2B). All nucleotide positions refer to the Human Genome, Feb 2009 Assembly (hg19). A square-shaped truncal build was evident (Figure 2B), as previously reported in four patients out of six by Steven et al. and two out of five by Doco-Fenzy et al.. The causative role of MYT1L haploinsufficiency for early-onset obesity is further reinforced by our finding, showing that our patient's proximal deletion breakpoint lies within a segment of 15,459 bp located in the sixth intron of MYT1L (Figure 2C). Our patient carrying a 2p25.3 deletion spanning nine genes, including SNTG2 and MYT1L (Figure 2B) manifests neither ASD nor aggressiveness and outburst.