Table 2.
Description of pathogenic variant, p.(Val667Met) LRP5 variant and variant of unknown significance.
| N° | Gene | cDNA | Protein | Gender | Age at first fracture (years) | Age at diagnosis (years) | Peripheral fractures | Vertebral fractures | LS-BMD (Z-score) | Other diseases |
|---|---|---|---|---|---|---|---|---|---|---|
| Pathogenic variant | ||||||||||
| 1 | ALPL | c.77C > T | p.(Pro26Leu) | F | 28.0 | 28.0 | Ribs, metacarpal | Yes | −2.8 | |
| 2 | COL1A1 | c.2792C > A | p.(Ala931Asp) | F | 32.0 | 50.0 | Yes | Yes | −3.4 | |
| 3 | COL1A2 | c.577G > A | p.(Gly193Ser) | M | 7.0 | 7.2 | No | Yes | −2.4 | |
| 4 | COL1A2 | c.3305G > C | p.(Gly1102Ala) | F | 2.0 | 7.9 | Radius-ulna, humerus | No | −2.0 | |
| 5 | COL1A2a | c.2821C > A | p.(Gln941Lys) | M | 10.0 | 28.0 | No | Yes | −2.4 | Auto-immune thyroiditis, prolactin adenoma |
| 6 | COL1A2 | c.1666G > A | p.(Gly556Ser) | F | 47.0 | 47.0 | No | Yes | −4.5 | |
| 7 | COL1A2 | c.946G > A | p.(Gly316Ser) | F | ND | 52.0 | No | Yes | −4.3 | Uveitis, otospongiosis, ankylosing spondylitis HLAB27- |
| 8 | DKK1b | c.359G > T | p.Arg120Leu | F | ND | 53.0 | Radius, metatarsal | No | −3.4 | |
| 9 | LRP5 | c.1425G > A | p.(Trp475*) | F | 5.0 | 5.9 | Radius-ulna | No | −0.7 | |
| 10 | LRP5 | c.2225 T > G | p.(Ile742Ser) | M | 3.0 | 8.8 | Tibia, femur, radius | No | −3.4 | |
| 11 | LRP5a | c.2273G > A | p.(Arg758Lys) | M | ND | 13.5 | Wrist, ankle | No | −1.9 | Spondylolisthesis L5-S1 |
| 12 | LRP5 | c.4105_4106delAT | p.(Met1369Valfs*2) | F | 47.0 | 47.0 | Pelvis | No | −4.9 | Auto-immune thyroiditis |
| 13 | LRP5 | c.4502C > T | p.(Pro1501Leu) | F | ND | 60.0 | Metatarsal | Yes | −3.7 | |
| 14 | LRP5 | c.1393G > A | p.(Ala465Thr) | M | 48.0 | 65.0 | No | Yes | −2.3 | |
| 15 | WNT1c | c.711_726del | p.(Thr238Alafs*150) | M | 7.0 | 7.3 | Femur | No | −3.7 | Charcot-Marie-tooth disease with normal mobility |
| 16 | WNT1 | c.403delG | p.Val135SerfsTer64 | M | 7.0 | 8.4 | Wrist, femur, fibula | Yes | −2.3 | Moderate asthma without treatment |
| 17 | WNT1 | c.962C > T | p.(Ala321Val) | F | 10.0 | 8.9 | Yes | −1.3 | Beta thalassemia | |
| 18 | WNT1 | c.610G > T | p.(Glu204*) | M | 52.0 | 44.0 | Yes | −3.0 | ||
| p.(Val667Met) LRP5 variant | ||||||||||
| 19 | LRP5 | c.1999G > A | p.(Val667Met) | F | 7.0 | 10.7 | Radius-cubitus, radius, femur | No | −2.8 | Learning difficulties, albinism |
| 20 | LRP5 | c.1999G > A | p.(Val667Met) | F | ND | 11.9 | No | Yes | −2.4 | Learning difficulties |
| 21 | LRP5 | c.1999G > A | p.(Val667Met) | F | 31.0 | 31.0 | Yes | Yes | −2.9 | |
| 22 | LRP5 | c.1999G > A | p.(Val667Met) | F | 16.0 | 35.0 | Femur | No | −2.5 | Migraine |
| 23 | LRP5 | c.1999G > A | p.(Val667Met) | M | 15.0 | 50.0 | Tibia, elbow, clavicula, ribs, phalanges | No | −2.0 | Breast cancer, mild form of inflammatory rheumatic disorders |
| 24 | LRP5 | c.1999G > A | p.(Val667Met) | M | 42.0 | 53.0 | No | Yes | −4.3 | |
| 25 | LRP5 | c.1999G > A | p.(Val667Met) | F | 54.0 | 54.0 | Femur | No | −2.7 | |
| Variant of unknown significance | ||||||||||
| 26 | COL1A1 | c.1875 + 3G > T | p.(?) | F | 20.0 | Femur | −2.1 | |||
| 27 | FKBP10 | c.926G > A | p.(Arg309His) | F | 42.0 | 42.0 | Ribs | No | −4.7 | |
| 28 | LRP5 | c.3977G > A | p.(Arg1326His) | F | ND | 46.0 | No | No | −3.4 | Mild form of rheumatoid arthritis |
| 29 | RANK | c.718A > G | p.(Lys240Glu) | F | 2.0 | 9.8 | Wrist, radius, femur, radius | No | −2.1 | Moderate asthma without treatment, pyelonephritis |
| 30 | RANK | c.1660A > G | p.(Thr554Ala) | M | 7.0 | 11.9 | Elbow, radius | No | −2.0 | Horseshoe kidney |
| 31 | RANK | c.544G > A | p.(Val1182Ile) | M | ND | 41.0 | No | Yes | −3.4 | |
| 32 | WNT1 | c.1013C > T | p.(Thr338Met) | M | 15.0 | 15.9 | Tibia | No | −2.4 | Algodystrophy |
| 33 | WNT1 | c.793C > A | p.(Arg265Ser) | F | 52.0 | 52.0 | Ribs | No | −4.0 | Breast cancer, low-grade chondrosarcoma |
LS-BMD: lumbar spine BMD; ND: non-determined; VUS: variant of unknown significance.
a
Associated with a p.(Val667Met) LRP5 variant.
b
Associated with a VUS in ALPL gene (c.1574delG, p.(Ter525=)).
c
Associated with a VUS in OPG gene (c.1012G > A, p.(Asp338Asn)).