Figure 3. Discovery of novel microdeletions associated with genomic disorders.
(A) A novel microdeletion on chromosome 15q25.2q25.3. Array CGH analysis for three individuals with a 660 kbp (chr15:82,889,423–83,552,890) deletion is shown. This microdeletion maps within a genomic hotspot flanked by high-identity SD blocks. Intrachromosomal SDs of high similarity relevant to this hotspot region are depicted as red (69.8 kbp, 98.6% identity) and green (17.6 kbp, 98.6% identity) block arrows. Note that the directly orientated SDs (red block arrows) likely mediate the underlying 15q25 rearrangements by non-allelic homologous recombination (NAHR). This region also contains a 60 kbp (chr15:82,775,465–82,835,495) gap in the current builds (build36 and build37) of the reference genome assembly. (B) Atypical 17q21.31 microdeletions refine critical interval genes. High-density array CGH for the 17q21.31 microdeletion region is shown for three individuals. Probes with log2 ratios below a threshold of 1.5 standard deviations from the normalized mean log2 ratio denote deletions (red). The typical deletions (top panel) were identified in 23 individuals while atypical deletions were identified in three individuals. Note that the smallest deletion (blue box) refines the phenotype-associated critical region (chr17:41,356,798–41,631,306) to encompass only five RefSeq genes. (C) Photographs of two individuals (9888884 and 648) with atypical deletions are shown. Patient #9888884 is a 5-year-old female child with clinical features typical of 17q21.31 microdeletion syndrome and includes distinctive dysmorphic features with a bulbous nasal tip, upslanting and almond-shaped palpebral fissures, long face, strabismus, epicanthal folds, and prominent ears; DD with limited speech; hypotonia in infancy; and a friendly disposition. Additional features are low birth weight, short stature, microcephaly, long fingers, and heart defects. She also presented with postaxial polysyndactyly, neonatal cholestasis, resolved leucopenia, dry skin with some hyperpigmented lesions, and an anteriorly split tongue. Patient #648 is 9-year-old male child and has a clinical history of generalized hypotonia, seizures, autism, mental retardation, motor DD, and dysmorphic features consistent with the 17q21.31 microdeletion syndrome (epicanthal folds; ptosis; long, pear-shaped nose; long, tapering fingers). Informed consent was obtained to publish the photographs.