Use of array CGH to detect exonic copy number variants throughout the genome in autism families detects a novel deletion in TMLHE

• DOI: 10.1093/hmg/ddr363
• Publication Date: 2011-08-25T02:15:43Z
• Authors: Patricia B.S. Cel...; Chad A. Shaw; Stephan J. Sanders; Jian Li; Michael T. Murtha; A. Gulhan Ercan-S...; Lea Davis; Susanne Thomson; Tomasz Gambin; A. Craig Chinault; Zhishuo Ou; Jennifer R. German; Aleksandar Milosa...; James S. Sutcliffe; Edwin H. Cook; Pawel Stankiewicz; Matthew W. State; Arthur L. Beaudet
• Keywords: Comparative genomic hybridization; Proband; genomic DNA

Autism is a neurodevelopmental disorder with increasing evidence of heterogeneous genetic etiology including de novo and inherited copy number variants (CNVs). We performed array comparative genomic hybridization using custom Agilent 1 M oligonucleotide intended to cover 197 332 unique exons in RefSeq genes; 98% were covered by at least one probe 95% three or more probes the focus on detecting relatively small CNVs that would implicate single protein-coding gene. The study group included 99 trios from Simons Simplex Collection. analysis identified validated 55 potentially pathogenic CNVs, categorized as autosomal heterozygous, homozygous autosomal, complex hemizygous deletions X chromosome probands. Twenty percent (11 55) these CNV calls rare when compared Database Genomic Variants. Thirty-six (20 also detected same samples an independent Illumina single-nucleotide polymorphism array. Findings note common sometimes 61 bp exonic deletion SLC38A10, found lymphoblast-derived DNA but not present whole-blood derived and, most importantly, male proband, TMLHE (trimethyllysine hydroxylase epsilon) encodes first enzyme biosynthesis carnitine. Data for lymphoblasts absent fresh blood suggest represent clonal outgrowth individual B cells pre-existing somatic mutations rather than artifacts arising cell culture. GEO accession GSE23765 (http://www.ncbi.nlm.nih.gov/geo/, date last accessed 30 August 2011). Genboree accession: http://genboree.org/java-bin/gbrowser.jsp?refSeqId=1868&entryPointId=chr17&from=53496072&to=53694382&isPublic=yes, 2011.