PMC4266984_01
Proband phenotype and cytogenetic analysis. Proband at the age of 6 years and 7 months, showing (a) slender habitus with little subcutaneous fat and scars from the surgery for inguinal hernias; (b) cutis aplasia in midline scalp; (c) sparse hair, long face, high frontal hair line, sparse eyebrows and eyelashes, hypoplastic alae nasi, and low-set ears; and (d) shawl scrotum. (e) Partial GTG-banding karyotype of the patient showing normal and derivative chromosomes 2 and 19. (f) Normal and derivative chromosomes 2 and 19 showing FISH signals. Note the signal of 19q (orange) at the top of der(2), followed by the 2p (green) signal and the 2q (orange) signal at the end of the chromosome. der(19) shows only the 19p (green) signal. (g) Diagram illustrating the insertion of the segment from 19q13.12 to 19q13.43 in 2p25.3, with concomitant deletion of 19q13.11-q13.12.
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Fig1
The clinical findings are described in Figure 1a-d and Table 1. Karyotyping revealed a de novo rearrangement between chromosomes 2p25.3 and 19q13.1 (Figure 1e). FISH analysis with subtelomeric probes showed a signal of 19q on der(2), which retained the signal of 2p and 2q, whereas der(19) presented only the 19p signal (Figure 1f). Microarray analysis indicated a 2.49-Mb de novo deletion (arr[hg19] 19q13.11-q13.12 (33,565,628-36,055,467) x 1 dn), which was confirmed by quantitative PCR (see Additional file 1: Figure S1). To our knowledge, this is the first case of a 19q13 deletion derived from a chromosomal rearrangement, which probably involved three breakpoints in chromosome 19 (at q13.11, q13.12, and q13.4) and one breakpoint in 2p25.3 (Figure 1g).
PMC4266984_02
Schematic summary of the reported 19q13.11 microdeletions, according to the human genome assembly hg19 (GRCh37). An ideogram of Chr. 19q12-q13.12 is displayed at the top. The shaded region between the solid black lines represents the MOCR of approximately 324 kb ([hg19] chr19:35,111,811-35,436,076). The solid red line at the left indicates the deletion breakpoint of the patient reported by Forzano et al. ([hg19] chr19:34,957,764-34,983,674), which affects the last two exons of UBA2. The proximal breakpoint of the male patient reported by Gana et al. ([hg18]chr19:39,608,712-39,626,575) is indicated by a short dotted line; this deletion affects the last 11 exons of UBA2. The gene map is displayed at the bottom, and qPCR validation targets are circled. Patients are numbered according to Table 1, and deletions are indicated with grey (female) and black (male) bars; the size is indicated in parentheses. MXX is a 46,XX male; phi, male foetus aborted at the 28th week of gestation.
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Fig2
SCGB2B2 (Figure 2). SCGB2B2 is a member of the secretoglobin protein family whose function is unknown to date. The upstream gene UBA2 has also been proposed as a candidate for this syndrome, and it was also deleted in all of the reported male patients (Figure 2).
PMC4266984_03
Schematic summary of the reported 19q13.11 microdeletions, according to the human genome assembly hg19 (GRCh37). An ideogram of Chr. 19q12-q13.12 is displayed at the top. The shaded region between the solid black lines represents the MOCR of approximately 324 kb ([hg19] chr19:35,111,811-35,436,076). The solid red line at the left indicates the deletion breakpoint of the patient reported by Forzano et al. ([hg19] chr19:34,957,764-34,983,674), which affects the last two exons of UBA2. The proximal breakpoint of the male patient reported by Gana et al. ([hg18]chr19:39,608,712-39,626,575) is indicated by a short dotted line; this deletion affects the last 11 exons of UBA2. The gene map is displayed at the bottom, and qPCR validation targets are circled. Patients are numbered according to Table 1, and deletions are indicated with grey (female) and black (male) bars; the size is indicated in parentheses. MXX is a 46,XX male; phi, male foetus aborted at the 28th week of gestation.
13039_2014_61_Fig2_HTML.jpg
PMC4266984_03_13039_2014_61_Fig2_HTML.jpg
Fig2
SCGB2B2 (Figure 2). SCGB2B2 is a member of the secretoglobin protein family whose function is unknown to date. The upstream gene UBA2 has also been proposed as a candidate for this syndrome, and it was also deleted in all of the reported male patients (Figure 2).
PMC4266984_04