Cutis aplasia, facial dysmorphic features, congenital heart abnormalities and mental retardation in a child with a cryptic deletion in 19p13.3. H. Al-Kateb1, A. Hahn2, J. M. Gastier-Foster3,4, D. L. Thrush3, L. Jeng1, S. E. McCandless2, C. A. Curtis1 1) Univ Hosp Case Human Gen Lab, Case Western Reserve Univ, Cleveland, OH; 2) Univ Hosp Case Human Gen, Case Western Reserve Univ, Cleveland, OH; 3) Nationwide Children's Hospital, Columbus, OH; 4) The Ohio State University Columbus, OH.
Advances in technology have made it feasible to discover chromosomal microdeletions that are difficult to recognize by conventional chromosomal analysis. Here we report the use of chromosomal microarray, fluorescence in-situ hybridization (FISH), and molecular genetics techniques to delineate and characterize a de novo constitutional deletion within 19p13.3 in a girl with multiple congenital anomalies. Her phenotype includes cutis aplasia of scalp, structural heart abnormalities, macrocephaly, hypotonia, mild mental retardation, dysmorphic facies and conductive hearing loss. Review of the literature revealed a few case reports of larger deletions, most of which include the subtelomeric region, which appears to be intact in our patient. Initial microarray analysis (Signature Select 1.0) revealed a 6-BAC-clone deletion within 19p13.3 with an estimated deletion size of 1.612 Mb. FISH studies delineated the proximal deletion breakpoint to within BAC clone RP11-125C3 and the distal deletion breakpoint to a region within or near the proximal portion of BAC RP11-648B14. Using SNPs we determined that the deletion is of paternal origin and we refined the proximal deletion breakpoint by 50kb and confirmed the absence of BAC RP11-268O21, which is immediately proximal to RP11-648B14. Based on these findings, the deletion is estimated to be approximately 1.93 Mb, encompassing at least 72 genes. Two genes in the deleted region appear to be good candidates for the patients 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). Work to better define the breakpoints is ongoing, both to gain insight into the mechanism that led to this deletion and to correlate the genotype and phenotype of this patient.