Table 1.
Mutations in sporadic patients offspring of nonconsanguineous parents
| Lab family no. | Origin | Gene | Heterozygous mutation | Protein effect | Splicing variant | CADD V1.3 | SIFT | Polyphen | Mutation Taster | Population database frequencies | De novo | Novel | OI type/severity score |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 3 | Egypt | COL1A1 | c.1155+1G>A | p.? | Y | n.p. | I/6 | ||||||
| 8 | Egypt | COL1A1 | c.1155+1G>C | p.? | Y | n.p. | III/13 | ||||||
| 12 | Egypt | COL1A1 | c.1299+1G>C | p.? | Y | n.p. | I/10 | ||||||
| 18 | Egypt | COL1A2 | c.740G>T | p.Gly247Val | – | 25.2 | Del (0) | Prob dam (1.00) | Disease causing (1.0) | n.p. | Y | Y | III/15 |
| 33 | Ecuador | COL1A2 | c.1036G>A | p.Gly346Ser | – | 25.9 | Del (0) | Prob dam (1.00) | Disease causing (1.0) | n.p. | |||
| 39 | Spain | – | I | ||||||||||
| 46 | Spain | COL1A2 | c.1406G>C | p.Gly469Ala | – | 20.3 | Del (0) | Prob dam (0.999) | Disease causing (1.0) | n.p. | IV | ||
| 51 | Spain | COL1A2 | c.1009G>A | pGly337Ser | – | 26.5 | Del (0) | Prob dam (1.00) | Disease causing (1.0) | n.p. | Y | IV | |
| 54 | Spain | COL1A1 | c.3505G>A | p.Gly1169Ser | – | 26.4 | Del (0) | Prob dam (1.00) | Disease causing (1.0) | n.p. | Y | IV | |
| 71 | Spain | – | IV | ||||||||||
| 72 | Spain | SERPINF1 | Maternal allele: c.271_279dupGCCCTCTCG | p.Ala91_Ser93dup | – | AMR 0.0086% | III | ||||||
| SAS 0.0061% | |||||||||||||
| NFE 0.0045% | |||||||||||||
| Paternal allele: c.273_283+1del | p.? | Y | n.p. | Y | |||||||||
| 83 | Turkey | COL1A2 | c.1117G>C | p.Gly373Arg | – | 32 | Del (0) | Prob dam (1.00) | Disease causing (1.0) | n.p. | Y | ||
| 88 | Turkey | COL1A1 | c.2533G>A | p.Gly845Arg | – | 28.0 | Del (0) | Prob dam (1.00) | Disease causing (1.0) | n.p. | Y | ||
| 90 | Spain | WNT1 | c.1026delC | p.Glu343Serfs*50 | – | n.p. | Y | Early‐onset osteoporosis with fractures | |||||
| 1002 | Turkey | – | |||||||||||
| 1005 | Spain | IFITM5 | c.‐14C>T | p.Met1ext‐5 | – | n.p. | Y | V | |||||
| 1016 | Spain | IFITM5 | c.‐14C>T | p.Met1ext‐5 | – | n.p. | Y | V | |||||
| 1017 | Spain | COL1A1 | c.581G>A | p.Gly194Asp | – | 26.1 | Del (0) | Prob dam (1.00) | Disease causing (1.0) | n.p. | Y | Y | III |
| 1019 | Venezuela | COL1A2 | c.1073G>A | p.Gly358Asp | – | 32.0 | Del (0) | Prob dam (1.00) | Disease causing (1.0) | n.p. | Y | Y | III |
| 1027 | Spain | IFITM5 | c.‐14C>T | p.Met1ext‐5 | – | n.p. | Y | V |
Mutations were classified as novel, when absent from the LOVD database for OI and HGMD. Unknown protein effect: p.?. SIFT: Del: deleterious; Polyphen Prob dam: probably damaging. Allele frequencies were obtained from ExAC with the help of Alamut software. AMR: Hispano‐Americans; NFE: Non‐Finnish Europeans; SAS: South Asians. Variants not present in ExAC are indicated with n.p. OI type (Sillence et al. 1979; Glorieux et al. 2000) and severity score (Aglan et al. 2012) are reported when available. COL1A1: NM_000088.3; COL1A2: NM_000089.3; IFITM5: NM_001025295.2; SERPINF1: NM_002615.5; WNT1: NM_005430.3.