Figure 1
Identification of the Proximal 16p11.2 Microdeletion.
(A) Microarray-based comparative genomic hybridization (aCGH) results of chromosome 16 in the proband. The identified 16p11.2 deletion is highlighted in the chromosome view and enlarged. Red, black, and blue dots represent aCGH probes with log2 ratios less than −0.25, in between −0.25 and 0.25, and greater than 0.25, respectively. (B) Confirmation of the deletion by fluorescence in situ hybridization (FISH) using a BAC probe that hybridized to 16p11.2 (RP11-114A14) and a control probe that hybridized to the subtelomere of chromosome 16q (16qTEL013). (C) Illustration of the chromosome 16 ideogram with enlarged views from ∼29.2 to 30.3 Mb within cytoband 16p11.2. The location of the 533.9-kb deletion and FISH probe are noted in relation to the location of known human genes and transcripts from the University of California Santa Cruz (UCSC) Genes track (including gene predictions from RefSeq, Genbank, Consensus Coding Sequence [CCDS], and UniProt), Online Mendelian Inheritance in Man (OMIM) disease genes (with OMIM identification [ID] numbers), segmental duplications [color was used to distinguish level of similarity (gray: 90–98% similarity; yellow: 98–99% similarity; orange: >99%], and structural variants from the Database of Genomic Variants34 (blue bars representing copy number gain copy number variants [CNVs], red bars representing copy number loss CNVs, and brown bars representing both copy number gain and loss CNVs).
Table 1
Case Reports of PKD with Proximal 16p11.2 Microdeletions
| Patient | Reference | Year | Age at Onset (Years) | Movement Disorders | History of Seizure | Developmental Disability | Chromosomal Microarray Analysis | Microdeletion Size (kb) | Deletion Coordinates (hg18) | Treatment (response) |
|---|---|---|---|---|---|---|---|---|---|---|
| 1 | Lipton and Rivkin4 | 2009 | Infancy | PKD and dopa-responsive parkinsonism | Yes, infantile convulsions | Verbal learning disabilities | SNP array | 544.3 | Chr16:29560500–30104842 | CBZ (very good to PKD); levodopa 200 mg/day (resolution of parkinsonism) |
| 2 | Dale et al.6 | 2012 | 6 | PKD | No | Speech delay, mild orobuccal dyspraxia | aCGH | 432.0 | Chr16:29581455–30013488 | No information |
| 3 | Dale et al.5,6 | 2011,2012 | 10 | PKD | Yes, benign infantile seizures | Mild intellectual disability | aCGH | 597.8 | Chr16:29500284–30098069 | No information |
| 4 | Weber et al.7 | 2013 | Infancy | PKD | Yes, infantile convulsions | Mainly speech delay, and impaired fine motor skills and balance | SNP array | 895.0 | Chr16: 29210745–30105652 | No information |
| 5 | Current case | 2014 | 10.5 | PKD | No | Asperger’s syndrome (language delay) | CGH + SNP array | 533.9 | Chr16:34656524–34827038 | CBZ (very good) |
Video 1.
Segment 1: This home video demonstrated an episode with truncal dystonia, seen as twisting of his trunk, while the patient is standing and holding a chair. The duration of the episode in the video lasted less than 5 seconds, but the episode was not captured from the outset. Segment 2: This home video demonstrated dystonia of bilateral upper extremities and trunk, seen as truncal flexion. The episode lasted less than 5 seconds but it was not captured from the outset.