Clinical and molecular characterization of a de novo 19p13.3 microdeletion

Abstract

Background: Structural rearrangements of chromosome 19p13.3 are a rare condition, and their phenotypic consequences remain not well defined, because of the variability of clinical manifestations. Increasing knowledge of new 19p13.3 microdeletion is useful to clarify the phenotypic variability observed in some patients. In a small number of recent papers, patients with intellectual disabilities, multiple congenital anomalies and microdeletion of the chromosome band 19p13.3 have been described. However, little is known about genes responsible for clinical features in patients carriers of 19p13.3 microdeletion; thus, increasing number of reported cases will be helpful to investigate the contribution of candidate genes, providing bases for future investigations.

Case presentation: Here, we report on a 10-years-old girl referred to our genetics clinic due to intellectual disability, attention deficit, behavioral and speech delay, hypotonia, facial dysmorphisms, eye anomalies and congenital malformations. Using an high resolution SNP array, we identified a de novo microdeletion of chromosome 19p13.3, resulting in the heterozygous loss of 27 RefSeq genes and a miRNA, partially overlapping with three others deletions already reported in literature, but extending downstream (centromeric) for additional 386 Kb. This chromosomal region includes 13 genes amongst of which we suggest for the first time the APC2, PLK5 and MBD3 genes as potential functional candidates for neurodevelopmental and behavioral phenotypes observed.

Conclusions: Here we describe a patient with a 19p13.3 microdeletion that spans to the downstream chromosomal region with respect to the overlapping deletions previously reported in several other cases. The neurobehavioral features observed in our case has extended the phenotypic spectrum associated with the 19p13.3 microdeletion. New candidate genes are proposed for the neurobehavioral phenotype observed in our case.

Keywords: 19p13.3 microdeletion; Intellectual disabilities; SNP-Array analysis.

Fig. 1

Facial phenotypes (frontal and lateral view) of the patient described in detail in the text

Fig. 2

a Microarray-based copy number analysis performed with the Affymetrix Genome Wide Human SNP 6.0 array and visualized using the Affymetrix Genotyping Console Browser. Copy number state of each probe is drawn along chromosome 19 from 0 to 7,000,000 bp. The upper panel represents the copy number state of the proband, the middle panel the father and the lower panel the mother. Values of Y-axis indicate the inferred copy number according to probe intensities. Red bar is the deleted region identified in the patient. b Localization of overlapping deletions identified in our patient and in patients already described in literature