Table 1 Summary of the clinical and molecular findings of studied subjects
From: Delineation of dual molecular diagnosis in patients with skeletal deformity
Case number | Case ID | Age | Sex | Inheritance | Clinical diagnosis | Gene | Molecular diagnosis | Zygosity |
|---|---|---|---|---|---|---|---|---|
Case 1 | SCO2003P1972 | 7 | M | AD | CS II | POGZ | White–Sutton syndrome | Het |
| Â | Â | Â | Â | Â | Â | FBN1 | Marfan syndrome | Het |
Case 2 | SCO1908P0067 | 18 | M | AD | AIS | COL1A1 | Osteogenesis imperfecta | Het |
| Â | Â | Â | Â | Â | Â | FBN1 | Marfan syndrome | Het |
Case 3 | PCT2007P0019 | 8 | F | AD | NFS | NF1 | Neurofibromatosis, type 1 | Het |
| Â | Â | Â | Â | Â | Â | COL1A1 | Osteogenesis imperfecta | Het |
Case 4 | SSS2008P0037 | 6 | M | AD | GHD | ANKRD11 | KBG syndrome | Het |
| Â | Â | Â | Â | Â | Â | COL11A1 | Marshall syndrome | Het |
Case 5 | SSS1910P0094 | 8 | F | AD | ISS | NF1 | Neurofibromatosis, Type 1 | Het |
|  |  |  |  |  |  | GLI2 | Culler–Jones syndrome | Het |
Case 6 | SSS2010P0110 | 12 | F | AD | ISS | TP63 | Rapp-Hodgkin syndrome | Het |
| Â | Â | Â | Â | Â | Â | PTPN11 | Noonan syndrome | Het |
Case 7 | RDD2001P0005 | 2 | M | AD | Arthrogryposis | FBN2 | Beals syndrome | Het |
| Â | Â | Â | Â | Â | Â | ANKRD11 | KBG syndrome | Het |
Case 8 | P19009402 | 4 | M | AD | Syndactyly | FGFR2 | Apert syndrome | Het |
| Â | Â | Â | Â | Â | Â | RYR1 | Malignant hyperthermia susceptibility 1 | Het |
Case number | Transcript numbers | Origin | Variant type | Variant | GnomAD frequency | Gerp++ | CADD | Patient phenotype |
|---|---|---|---|---|---|---|---|---|
Case 1 | NM_015100.3 | De novo | Frameshift | c.1180_1181del p.(Met394ValfsTer9) | 0 | 3.36 | NA | Ocular hypertelorism; intellectual disability; scoliosis; congenital dislocation of hip joint |
|  | NM_000138.4 | Maternal | Nonsense | c.2649G > A p.(Trp883Ter) | 0 | 5.33 | 38 |  |
Case 2 | NM_000088.3 | De novo | Nonsense | c.1081C > T p.(Arg361Ter) | 0 | 3.97 | 37 | Bone fragility; scoliosis; osteopenia |
|  | NM_000138.4 | Maternal | Missense | c.1453C > T p.(Arg485Cys) | 0 | 5.33 | 32 |  |
Case 3 | NM_000267.3 | Paternal | Frameshift | c.2307del p.(Thr770LeufsTer21) | 0 | 5.25 | 18.24 | Cafe´-au-lait macules; scoliosis; bone fragility; blue sclera |
|  | NM_000088.3 | Paternal | Splicing | c.2028+ 4 A > G | 0 | NA | NA |  |
Case 4 | NM_013275.5 | De novo | Nonsense | c.4750G > T p.(Glu1584Ter) | 0 | 5.08 | 48 | Short stature; depressed nasal bridge; long philtrum; low-set ears; tongue thrusting |
| Â | NM_001854.3 | Paternal | Frameshift | c.2508dup p.(Leu837ThrfsTer81) | 0 | NA | NA | Â |
Case 5 | NM_000267.3 | NA | Splicing | c.6705–1 G > A | 0 | 5.59 | 18 | Scoliosis; short stature; abnormality of the cerebral white matter; cafe-au-Lait macules |
| Â | NM_005270.4 | NA | Frameshift | c.1189del p.(Val397CysfsTer124) | 0 | NA | NA | Â |
Case 6 | NM_003722.4 | NA | Nonsense | c.109C > T p.(Arg37Ter) | 0 | 3.84 | 22.7 | Short stature; low set ear; low posterior hairline; scoliosis; hyperpigmentation; webbed neck |
|  | NM_002834.3 | NA | Missense | c.1510A > G p.(Met504Val) | 0 | 5.13 | 25.6 |  |
Case 7 | NM_001999.3 | Paternal | Missense | c.3437A > G p.(Tyr1146Cys) | 0 | 5.13 | 18.69 | Joint contractures; atrial septal defect; clinodactyly of fingers |
| Â | NM_013275.5 | De novo | Frameshift | c.3024_3025del p.(Lys1009GlyfsTer8) | 0 | NA | NA | Â |
Case 8 | NM_000141.4 | De novo | Missense | c.755C > G p. (Ser252Trp) | 0 | 5.79 | 23.5 | Cloverleaf skull; orbital hypertelorism; proptosis; midfacial hypoplasia; syndactyly of the hands and feet; malignant hyperthermia |
|  | NM_000540.2 | Paternal | Frameshift | c.12788_12793dup p.(Glu4263_Gly4264dup) | 3.36 × 10–5 | NA | NA |  |