PMC4005632_01
Photographs of proband and his mother. Proband (left) and his mother (right) showing lower facial weakness, hypertelorism, and downward slanting palpebral fissures.
1755-8166-7-27-1.jpg
PMC4005632_01_1755-8166-7-27-1.jpg
F1
The proband presented at 9 years of age with developmental delay, autism spectrum disorder, speech delay, attention deficit hyperactivity disorder, and a variety of physical abnormalities: short stature (10th percentile for the proband and <1st percentile for the mother), mild macrocephaly in relation to body size, metacarpal and metatarsal anomalies, flat feet, lower facial weakness, hypertelorism, downward slanting palpebral fissures, frequent dental caries, and digit anomalies including brachydactyly, wide nail beds, deviation of fourth digits to the ulnar side, radially displaced thumbs, and mild clinodactyly (Figures 1 and 2).
Radiographs showing digit anomalies of the proband. Anomalies included brachydactyly, wide nail beds, deviation of fourth digits to the ulnar side, radial displacement of thumbs, and clinodactyly of the fourth and fifth digit tarsal.
1755-8166-7-27-2.jpg
PMC4005632_01_1755-8166-7-27-2.jpg
F2
The proband presented at 9 years of age with developmental delay, autism spectrum disorder, speech delay, attention deficit hyperactivity disorder, and a variety of physical abnormalities: short stature (10th percentile for the proband and <1st percentile for the mother), mild macrocephaly in relation to body size, metacarpal and metatarsal anomalies, flat feet, lower facial weakness, hypertelorism, downward slanting palpebral fissures, frequent dental caries, and digit anomalies including brachydactyly, wide nail beds, deviation of fourth digits to the ulnar side, radially displaced thumbs, and mild clinodactyly (Figures 1 and 2).
PMC4005632_02
Pedigree: The proband (III4) has five half-brothers (III1, III2, III3, III5 and III6) resulting from his mother's four different marriages. The proband (III4), his mother (II4) and one of his half-brothers (III3) harboring a 516 kb duplication at 13q13.3 (red small circle) showed dysmorphic facial features, lower facial weakness, and relative macrocephaly (blue square) as well as digit anomalies including clinodactyly, brachydactyly, and short stature (green square). Developmental delay (red square) and autism (Yellow Square) were observed in all six brothers. The mother showed all of the above abnormalities except autism.
1755-8166-7-27-3.jpg
PMC4005632_02_1755-8166-7-27-3.jpg
F3
The proband had five half-brothers resulting from his mother's four different marriages (Figure 3). Developmental delay and autism were observed in all six brothers and thus were not exclusive to those harboring the 13q31.3 duplication, although they might have been maternally inherited (Figure 3).
Duplication of 13q31.3. A. Chromosome 13 with duplication at 13q31.3. B. Proband SNP-array results, including the log2 ratio, weighted log2 ratio, copy number state, and the genes at the duplicated region. C. Database of genomic variants showing 515.6 kb duplication at chromosome 13, position 91,989,261 to 92, 504,857, including miR-17 ~ 92 and five exons of the GCP5 gene.
1755-8166-7-27-4.jpg
PMC4005632_02_1755-8166-7-27-4.jpg
F4
This analysis detected a microduplication of 516 kb at 13q31.3 (Figure 4), which encompassed the miR-17 ~ 92 cluster genes (MIR17, MIR18A, MIR19A, MIR20A, MIR19B1, MIR92A1) and the first five exons of the GPC5 gene.