Copy number imbalances involving ARID1Bin patients with short stature and developmental disorder
Four thousand four hundred eleven individuals in the clinical population met our inclusion criteria (as described in methods), including 415 patients with short stature, 196 patients with tall stature and 3800 patients with normal stature. Three individuals with copy number variants encompassing ARID1B were identified among 415 patients with short stature who underwent clinical microarray analysis at Boston Children’s Hospital. The locations of the two deletions and one duplication in relation to the ARID1B gene are shown in Fig. 1.
Fig. 1 Three individuals with copy number variants encompassing ARID1B shown as tracks in the UCSC genome browser
Figure 1
Red tracks indicate deletion and blue track indicates duplication. The numbers associated with each track are the Z-scores of patient’s height.
The first patient (patient A) carries a 658 kb de novo deletion at 6q25.3 which affected only ARID1B; the second patient (patient B) carries a 6.8 Mb de novo deletion at 6q25.1-q25.3 which overlaps with the deletion in Patient 1. The height Z-score for both patients are -2.3 and -2.1 respectively. The patient with the duplication (patient C) was a 13-year-old Caucasian girl who carries a 207 Kb maternally inherited intragenic duplication at 6q25.3. Her height Z-score was -2.7. The mother’s height is below average (Z = -0.33) but not short. In addition to short stature, all three patients exhibited language impairment, facial malformation and intellectual disability. Thus all three patients exhibited syndromic short stature. Detailed clinical phenotypes and their growth curves can be found in Additional files 1 & 2.
There were no CNVs involving ARID1B in 3800 patients with normal stature and 196 patients with tall stature in our clinical population.