Ribosomal protein gene deletions and associated clinical findings in patients with DBA
| ID . | Region (hg18)* . | Size . | Gene . | Sex . | Age . | Hgb/Hct . | Retic . | eADA . | MCV . | Steroid response . | Physical abnormality . | Other . | Confirmed by aCGH . |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1382 | chr19:46620492-47448185 | 828 kb | RPS19 | F | 1 mo | 2/6 | 0.1 | — | — | N | Macrocephaly, developmental delay | MS-BMT at 2.5 y | Yes |
| 1687 | chr19:46898790-47275854 | 377 kb | RPS19 | F | 0 mo | 1.7/5.9 | 0 | — | 95.1 | N | VSD | Yes | |
| 1178 | chr12:54715842-54731191 | 15 kb | RPS26 | M | 3.5 mo | 3.5/9.7 | 0.6 | — | 110 | Y | None | Yes | |
| 842 | chr12:54643476-54728995 | 85 kb | RPS26 | M | 7 mo | 7.2/20.5 | 0.8 | — | 105.8 | Y | None | Remission as teenager | Not tested |
| 886 | chr15:81011018-82589310† | 1.5 Mb | RPS17 | F | 0 mo | 7.6/— | — | — | — | Y | None | Yes | |
| 1314 | chr15:81011018-82623936† | 1.6 Mb | RPS17 | F | 2 mo | 2.6/— | — | ↑ | — | Y | PFO, short stature | Initially steroid responsive, currently transfusion dependent | Not tested |
| 20QL | chr15:81011018-82623936† | 1.6 Mb | RPS17 | M | 2.5 mo | 2.1/— | — | — | — | N | Short stature | Yes | |
| 802 | 3q21-tel | Variable | See¶ | M | 2 y | 7.1/21 | 0.7 | 0.72 | 103 | Y | None | Neutropenia; remission at age 16‡ | N/A |
| 802-2 | 3q21-tel | Variable | See¶ | F | 2 mo | 2.6/7.4 | 0.1 | 1.17 | 90 | N | None | Neutropenia‡ | N/A |
| 80-3§ | — | — | — | F | 2 y | 10.4/ 30.4 | 1.7 | 1 | 93 | Y | None | Neutropenia; remission at age 12‡ | N/A |
| 1786 | 15q | Variable | See# | M | 2 mo | 4.3/12.5 | — | 1.01 | — | Y | None | Remission as teenager | N/A |
| ID . | Region (hg18)* . | Size . | Gene . | Sex . | Age . | Hgb/Hct . | Retic . | eADA . | MCV . | Steroid response . | Physical abnormality . | Other . | Confirmed by aCGH . |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1382 | chr19:46620492-47448185 | 828 kb | RPS19 | F | 1 mo | 2/6 | 0.1 | — | — | N | Macrocephaly, developmental delay | MS-BMT at 2.5 y | Yes |
| 1687 | chr19:46898790-47275854 | 377 kb | RPS19 | F | 0 mo | 1.7/5.9 | 0 | — | 95.1 | N | VSD | Yes | |
| 1178 | chr12:54715842-54731191 | 15 kb | RPS26 | M | 3.5 mo | 3.5/9.7 | 0.6 | — | 110 | Y | None | Yes | |
| 842 | chr12:54643476-54728995 | 85 kb | RPS26 | M | 7 mo | 7.2/20.5 | 0.8 | — | 105.8 | Y | None | Remission as teenager | Not tested |
| 886 | chr15:81011018-82589310† | 1.5 Mb | RPS17 | F | 0 mo | 7.6/— | — | — | — | Y | None | Yes | |
| 1314 | chr15:81011018-82623936† | 1.6 Mb | RPS17 | F | 2 mo | 2.6/— | — | ↑ | — | Y | PFO, short stature | Initially steroid responsive, currently transfusion dependent | Not tested |
| 20QL | chr15:81011018-82623936† | 1.6 Mb | RPS17 | M | 2.5 mo | 2.1/— | — | — | — | N | Short stature | Yes | |
| 802 | 3q21-tel | Variable | See¶ | M | 2 y | 7.1/21 | 0.7 | 0.72 | 103 | Y | None | Neutropenia; remission at age 16‡ | N/A |
| 802-2 | 3q21-tel | Variable | See¶ | F | 2 mo | 2.6/7.4 | 0.1 | 1.17 | 90 | N | None | Neutropenia‡ | N/A |
| 80-3§ | — | — | — | F | 2 y | 10.4/ 30.4 | 1.7 | 1 | 93 | Y | None | Neutropenia; remission at age 12‡ | N/A |
| 1786 | 15q | Variable | See# | M | 2 mo | 4.3/12.5 | — | 1.01 | — | Y | None | Remission as teenager | N/A |
ID indicates Diamond-Blackfan Anemia Registry identification number; Age, age at presentation; Hgb, hemoglobin (g/dL); Hct, hematocrit (%); Retic, reticulocyte percentage; eADA, erythrocyte adenosine deaminase activity (IU/g hemoglobin); MCV, mean corpuscular volume (fL); tel, telomere; —, data not available; ↑, reported as elevated; VSD, ventricular septal defect; and PFO, patent foramen ovale.
Regional copy variant boundaries as identified by SNP-Array/PennCNV.
The centromeric deletion boundary defined by SNP-array is conservative and does not include RPS17. The deletion boundaries identified by aCGH were 80 591 629-80 647 378 and 80 999 054-81 617 511 for sample 886 and 80 537 056-80 834 670 and 80 925 204-81 425 809 for sample 20QL. These deletion calls include both copies of RPS17 and may reflect the inability of hybridization probes to differentiate paired copies of RPS17.
All siblings have modest neutropenia (absolute neutrophil counts, 600-1200/mm3) without increased propensity for infection.
Clinical information for a second sibling is included although material for CNV analysis was not available for study.
RPL39L and RPL35A are located in the involved region on chromosome 3q; RPL35A is the only confirmed DBA gene in this region.
RPS17, RPS27L, RPS4, and RPLP1 are located on chromosome 15q; RPS17 is the only confirmed DBA gene in this region.