Molecular characterization of a novel, de novo, cryptic interstitial deletion on 19p13.3 in a child with a cutis aplasia and multiple congenital anomalies

Abstract

We report on a de novo constitutional deletion within G-band region 19p13.3 in a girl with cutis aplasia of the scalp, facial anomalies, structural heart abnormalities, hypotonia, mild mental retardation and conductive hearing loss which we characterized with chromosomal microarray, fluorescence in situ hybridization (FISH), and SNP analyses. Initial microarray analysis revealed a 6-BAC-clone deletion covering an approximately 1.612 Mb region within 19p13.3. Subsequent BAC FISH studies delineated the proximal deletion breakpoint to within BAC clone RP11-125C3 and the distal deletion breakpoint to within BAC clone RP11-648B14. SNP analysis showed the deletion to be of paternal origin and further refined its distal breakpoint to within a 20 kb region between rs11666694 and novel SNP2 that we identified at g.2,924,845, and its proximal deletion breakpoint to within a 22 kb region between rs35280644 and rs262562. Accordingly, the size of the deletion was revised to 1.89-1.932 Mb in length. We identified many Alu, L1, and L2 repeats, as well as SINE and LINE sequences at both deletion breakpoints. We found the deletion to encompass 71 genes, two of which appear to be good candidates for the patient's observed craniofacial and cardiac anomalies: guanine nucleotide binding protein (G protein), alpha 11 (Gq class)(GNA11), and Transducin-like Enhancer of Split 2 (E(sp1) homolog, Drosophila)(TLE2).