We identified 14 individuals with microdeletions of 3q29 amongst our patient population, including one family with a mildly affected mother and two affected children (Fig. ). We characterized 13 of the 14 deletions in more detail using a high-density oligonucleotide microarray (insufficient DNA was available for testing of the mother of the two affected children). Eleven individuals had typical 1.6 Mb deletions. Both BAC and oligo arrays confirmed that these eleven deletions had breakpoints flanked by segmental duplications known to mediate the common-sized microdeletion of 3q29 (Fig. ). Of the other deletions, one ~1.4 Mb deletion was within the common deletion region with only its proximal breakpoint flanked by LCRs, one ~1.5 Mb deletion overlapped the proximal end of the common deletion region by ~500 kb and extended more proximally, and one deletion > 3.2 Mb in size flanked the proximal end of the commonly deleted region (Fig. ). Neither the 1.5 Mb deletion nor the 3.2 Mb deletion has breakpoints flanked by LCRs. We confirmed a deletion in all 14 individuals by FISH. Of the eight individuals for whom parental samples were available for analysis, five had de novo abnormalities, all of which were the common-sized deletion. FISH also identified a deletion of 3q29 in the mother of the two siblings with microdeletion of 3q29. BAC microarray analysis of the father of the individual with the > 3.2 Mb proximal deletion showed the same deletion, indicating that the patient's deletion was paternally derived.
Figure 1 Summary of array CGH results on individuals with microdeletions and microduplications of 3q29. (A) Ideogram of chromosome 3 showing the location of the 3q29 cytogenetic band. (B) Representative SignatureChipWG result plot for an individual with a single (more ...)
Clinical information was available for seven individuals with the typical 1.6 Mb deletion (Table ). The clinical features common to three or more individuals in our cohort include microcephaly or small head, large low-set and posteriorly rotated ears, wide nasal bridge, and language delay. High-arched palate, widely spaced teeth, clumsy gait, head banging, macrocephaly, patent ductus arteriosus, chest cavity deformity, and hypospadias were identified in one or two individuals (Table ).
Summary of clinical features found in individuals with common-sized 3q29 microdeletion in this and previous studies.
We also identified 19 individuals with microduplications of 3q29 (Fig. ). We analyzed 17 of the 19 microduplications of 3q29 using the high-density 3q29 oligo array to refine the breakpoints (Fig. ). The high-resolution microarray identified 12 different duplication sizes that range in size from 200 kb to 2.4 Mb and which flank, span, or partially overlap the commonly deleted region. We also identified five cases which appear to be the reciprocal duplication product of the 3q29 microdeletion because they are flanked by the LCRs which mediate the common microdeletion of 3q29. Although five other microduplications of 3q29 have one breakpoint that is flanked by an LCR, only the reciprocal duplications have both breakpoints flanked by LCRs (Fig. ).
For the 10 individuals with 3q29 microduplications for whom parental DNA was available for microarray analysis, two had de novo abnormalities. The three reciprocal 3q29 duplications for which parental samples were available for testing were all inherited from a parent.
Clinical information was available for seven individuals with microduplications of 3q29, three of whom had the reciprocal product of the common-sized deletion. The only clinical feature common to these three individuals was mild to moderate mental retardation (Table ). Among individuals with microduplications of different sizes, craniosynostosis, high palate, seizures, and ventricular septal defect were each identified twice.
Summary of clinical features found in individuals with common-sized 3q29 microduplication in this and previous studies.