Introduction
Methods
Subjects
Mutation Analysis
Interferon Analysis
Results
Mutation Data
Patienta
| Gender | Country of origin | Consanguinity | Relationship to other patients in cohort | Mutation | Protein | Age at presentation (months (mo.)/years (yr.)) | Features at initial presentation | Current age in years |
---|---|---|---|---|---|---|---|---|---|
1 | Female | France | No | None | 11,544,822–11,556,767 del | p.Ex4_7 del Hom | 3 yr. | Seizures | Deceased at age 30 |
2 | Female | Austria | No | Sibling of 3 | c.369C > A/c.721G > A | p.Tyr123X Het./p.Asp241Asn Het. | 12 mo. | Delayed motor development | 13 |
3 | Male | Austria | No | Sibling of 2 | c.369C > A/c.721G > A | p.Tyr123X Het./p.Asp241Asn Het. | 3 yr. | AITP | 13 |
4 | Male | Turkey | Yes | Sibling of 5 | c.266C > T | p.Thr89Ile Hom. | 2 yr. | Spasticity & vasculitic skin rash | 17 |
5 | Female | Turkey | Yes | Sibling of 4 | c.266C > T | p.Thr89Ile Hom. | 14 yr. | Short stature | 20 |
6 | Male | Pakistan | Yes | None | c.667C > T | p.Gln223X Hom. | 8 mo. | Short stature | 17 |
7 | Male | India | Yes | None | 11,543,690–11,548,656 del | p.Ex5_7 del Hom | 2 yr. | Recurrent infections | 14 |
8 | Female | Portugal | Yes | Noneb
| c.791 T > A | p.Met264Val Hom. | 3 yr. | Recurrent infections | 34 |
9 | Female | Mali | Yes | None | c.643G > A | p.Gly215Arg Hom. | 6 yr. | Lupus nephropathy | 22 |
10 | Female | Egypt | Yes | None | c.772-790del | p.Ser258Trpfs*39 Hom. | 4 yr. | Leg pain | 17 |
11 | Male | France | Yes | None | c.821 T > C | p.Val274Ala Hom. | 2 yr. | Dev. delay & hypothyroidism | 14 |
12 | Female | Senegal | Yes | Sibling of 13 | c.643 g > a | p.Gly215Arg Hom. | 5 yrs. | Cerebral haemorrhage (AITP) | 7 |
13 | Male | Senegal | Yes | Sibling of 12 | c.643 g > a | p.Gly215Arg Hom. | 4 mo. | Metaphyseal lesions | 2 |
14 | Female | Turkey | Yes | Nonec
| c.155 A > C | p.Lys52Thr Hom. | 6 yrs. | Bruising & petechia (AITP) | 12 |
15 | Female | Mexico | Yes | None | c.725 A > G | p.His242Arg Hom. | 3 yrs. | Short stature & leg bowing | 16 |
16 | Female | Turkey | Yes | Sibling of 17 | c.155 A > C/c.790 A > G | p.Lys52Thr Hom./p.Met264Val Het. | 2.5 yrs. | AIHA | 15 |
17 | Male | Turkey | Yes | Sibling of 16 | c.155 A > C/c.790 A > G | p.Lys52Thr Hom./p.Met264Val Het. | 3 mo. | Short stature & AIHA | 13 |
18 | Female | Iraq (Jewish) | Yes | Noned
| c.325G > A | p.Gly109Arg Hom. | 2 yrs. | Short stature | 36 |
19 | Female | Lebanon | Yes | Sibling of 20 | c.389 + 1G > A | p.? Hom. | 9 yrs. | Jaundice (Hepatitis) | 10 |
20 | Female | Lebanon | Yes | Sibling of 19 | c.389 + 1G > A | p.? Hom. | Birth | AITP | Deceased at less than 1 year |
21 | Male | Italy | Yes | None | c.359 A > G | Gln120Arg Hom. | 1 mo. | AITP | 9 |
22 | Male | Israel (Arabic) | Yes | Nonee
| c.325G > A | p.Gly109Arg Hom. | 15 yrs. | Short stature & spasticity | 35 |
23 | Male | China | No | Sibling of 24, cousin of 25 & 26 | c.325G > A/c.712 T > C | p.Gly109Arg Het./p.Cys238Arg Het. | 5 yrs. | Short stature | 12 |
24 | Female | China | No | Sibling of 23, cousin of 25 & 26 | c.325G > A/c.712 T > C | p.Gly109Arg Het./p.Cys238Arg Het. | 7 mo. | Short stature & motor delay | 7 |
25 | Female | China | No | Sibling of 26, cousin of 23 & 24 | c.131C > T/c.712 T > C | p.Thr44Met Het./p.Cys238Arg Het. | 6 mo. | Short stature | 10 |
26 | Female | China | No | Sibling of 25, cousin of 23 & 24 | c.131C > T/c.712 T > C | p.Thr44Met Het./p.Cys238Arg Het. | 6 mo. | Short stature | 15 |
Clinical Data
Skeletal Manifestations
Patient1
| Last recorded height as SD below the mean (age at assessment) | Metaphyseal dysplasia | Platyspondyly | Intracranial calcification | Cranial MRI manifestations | Spasticity | Developmental delay (Degree) |
---|---|---|---|---|---|---|---|
1 | 4 (23) | Yes | Yes | Yes | Periventricular white matter changes | No | Yes (Mod.) |
2 | 5.5 (12) | Yes | Yes | No | No | Yes | Yes (Mild) |
3 | 2.5 (12) | No | Yes | NA | NA | No | No |
4 | 4.3 (16) | Yes | Yes | Yes | No | Yes | No |
5 | 3.8 (19) | Yes | Yes | Yes | Nil beyond changes associated with calcification | Yes | No |
6 | 5 (13) | Yes | Yes | Yes | Ischaemic lateral ventricle lesions | Yes | Yes (Mod.) |
7 | 3 (8) | Yes | Yes | Yes | Subcortical parietal granuloma (TB reaction) | No | No |
8 | 4 (18) | Yes | Yes | NA | NA | No | No |
9 | 6.5 (18) | Yes | No | Yes | No | No | No |
10 | 3 (13) | Yes | Yes | NA | No | Yes | No |
11 | 2 (12) | Yes | Yes | No | Ventricular dilatation | Yes | Yes (Severe) |
12 | 2 (6) | Yes | Yes | Yes | Left subdural fronto-parietal subacute to chronic bleed; multiple petechial bilateral intra-parenchymal lesions | Yes | No |
13 | 0 (0.5) | Yes | Yes | No | NA | No | No |
14 | 2.5 (10) | Yes | Yes | NA | No | No | No |
15 | 6 (12) | Yes | Yes | NA | NA | No | No |
16 | 4 (12) | Yes | Yes | NA | NA | No | No |
17 | 3 (10) | Yes | Yes | NA | No | No | No |
18 | 3.5 (36) | Yes | Yes | No | NA | Yes | No |
19 | 2.5 (10) | Yes | Yes | NA | Developmental venous anomaly associated with 3 mm pontine cavernoma | No | Yes (Mild) |
20 | NA | NA | NA | NA | NA | NA | NA |
21 | 3 (10) | Yes | Yes | Yes | Leukodystrophy in the internal capsule of the semioval centre | Yes | Yes (Mild) |
22 | 5.5 (35) | Yes | Yes | Yes | NA | Yes | Yes (Mod.) |
23 | 2 (12) | Yes | Yes | NA | No | No | No |
24 | 3 (7) | Yes | Yes | NA | No | Yes | No |
25 | 3.5 (10) | Yes | Yes | NA | NA | No | No |
26 | 5 (15) | Yes | Yes | NA | NA | No | No |
Total | 0–6.5 | 24/25 (1 NA) | 24/25 (1 NA) | 9/14 (12 NA) | 8/16 (10 NA) | 11/25 (1 NA) | 7/25 (1 NA) |
1.8–4.2 | 15/15 | 14/15 | 6/8 (7 NA) | 2/3 (13 NA) | 4/14 (1 NA) | 4/14 (1 NA) |
Neurological Manifestations
Immune Manifestations
Autoimmune Manifestations
Patient1
| Antinuclear antibodies (fluorescence, titre) | Anti-dsDNA antibodies (titre) | Serum IFNα >2 IU/ml | ISG Score positive (>2.466) | Raynaud’s phenomenon (RP) or vasculitis | AITP (Anti-platelet abs) | AIHA | Juvenile idiopathic arthritis | SLE | Renal disease | Hypo- thyroidism | Biopsy proven autoimmune hepatitis |
---|---|---|---|---|---|---|---|---|---|---|---|---|
1 | Yes (Nuclear dots & diffuse cytoplasmic, 1:1280) | No | Yes | Yes (40.034, 49.393) | Yes (vasculitis) | No | No | No | No | Yes | Yes | No |
2 | Yes (Homogenous,1:640) | Yes (1:320) | Yes | NA | No | No | No | No | Yes | Yes | Yes | No |
3 | Yes (Homogenous,1:5120) | Yes | Yes | Yes (13.931) | No | Yes | No | No | No | Yes | No | No |
4 | Yes (1:640) | Yes (100 Farr IU/ml) | Yes | Yes (14.826, 21.388) | Yes (vasculitis) | No | No | No | Yes | Yes | No | No |
5 | Yes (1:160) | No | Yes | Yes (3.756, 30.404) | Yes (RP) | No | No | No | No | No | No | No |
6 | Yes (>1:320) | Yes (1:1280) | Yes | Yes (71.094) | No | No | Yes | No | No | No | No | No |
7 | Yes (Strongly positive on immunoblot) | Yes (strongly positive on immunoblot) | NA | NA | No | Yes (Abs) | No | Yes | Yes | Yes | No | No |
8 | Yes (1:1280) | Yes (>500 Farr IU/ml) | NA | NA | No | Yes | No | No | Yes | No | Yes | No |
9 | Yes (1:1600) | Yes (121, n < 100 ELISA) | Yes | Yes (34.120) | No | Yes (Abs) | Yes | No | Yes | Yes | No | No |
10 | Yes (Speckled, 1:640) | Yes (33, n < 20 ELISA) | Yes | NA | No | No | No | No | No | Yes | No | No |
11 | Yes (Speckled, 1/200) | NA | NA | NA | No | Yes | No | No | No | No | Yes | No |
12 | Yes (1/200) | No | Yes | NA | No | Yes (Abs) | No | No | No | No | No | No |
13 | Yes (1/400) | Yes | Yes | NA | No | No | No | No | No | No | No | No |
14 | Yes (1:640) | Yes | NA | NA | No | Yes | No | No | No | No | Yes | No |
15 | Yes (Speckled, 1:80) | No | NA | NA | No | No | No | Yes (RF pos.) | No | No | No | Yes |
16 | No | No | NA | Yes (24.839) | No | No | Yes | No | No | No | No | No |
17 | Yes (Homogenous, 1/100)
| Yes (1.78 index, n ≥ 1.1 positive) | NA | Yes (24.815) | Yes (RP) | No | Yes | No | Yes | Yes | No | No |
18 | NA | NA | NA | Yes (2.77) | No | No | No | No | No | No | No | No |
19 | Yes (Homogenous, 1/2560) | Yes (10 k IU/L) | NA | NA | No | No | No | No | No | No | No | Yes |
20 | NA | NA | NA | NA | NA | Yes | No | NA | NA | NA | NA | NA |
21 | Yes (Homogenous, 1:640) | Yes (1:640) | NA | No (0.725, 0.6) | No | Yes (No abs) | No | No | Yes | Yes | No | No |
22 | NA | NA | NA | No (0.770) | No | No | No | No | No | No | No | No |
23 | Yes (Homogenous, 1:640) | Yes (>90, n < 7 IU/ml) | NA | NA | No | Yes | Yes | No | Yes | Yes | No | LFTs abnormal, biopsy pending |
24 | NA | NA | NA | NA | No | Yes | No | No | No | No | No | LFTs abnormal, biopsy pending |
25 | Yes (Homogenous, >2560, n < 40) | Yes (15, n < 7 IU/ml) | NA | NA | No | Yes | Yes | No | Yes | No | No | Yes |
26 | Yes (Homogenous, 640, n < 40) | No | NA | NA | No | No | Yes | No | No | No | No | LFTs abnormal, biopsy pending |
Total | 21/22 (4 NA) | 15/21 (5 NA) | 10/10 (16 NA) | 9/11 (15 NA) | 4/25 (1NA) | 12/26 | 7/26 | 2/25 (1 NA) | 9/25 (1 NA) | 10/25 (1 NA) | 5/25 (1 NA) | 3/25 (1 NA) |
7/14 (1 NA) | NA | 5/5 10 NA | 1/1 14 NA | 1/14 1 NA | 6/14 (1 NA) | 3/14 (1 NA) | 2/14 (1 NA) | 5/14 (1 NA) | 4/14 (1 NA) | 1/14 (1 NA) | 0/14 (1 LFT abnormal) (1 NA) |
Manifestation of Immunodeficiency
Patients1
| History of recurrent infection | Medication at time of assay | IgG g/L | IgM g/L | IgA g/L | Lympho-cyte count | Neutrophil count |
CD3 (T-cells) | CD4+/CD3+ | CD8+/CD3+ | CD19 (total B cells) | CD56 & CD16 (NK cells) | CD3% | CD4+/CD3+ % | CD8+/CD3+ % | CD19% | CD56 & CD16% |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
1 | No | Methotrexate | N | N | N |
1000 /mm3 (2500–7200) |
1000 /mm3 (1500–8000) | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
2 | No | Mycophenol-ate mofetil & prednisolone |
5.1 (7.2–14.8) |
0.31 (0.7–2.8) | 0.55 (0.5–2.6) |
3 g/L (4.5–13.5) |
1.6 g/L (2–7) | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
3 | No | Prednisolone | NA | NA | NA | 5.5 g/L (4.5–13.5) | 2.5 g/L (2–7) | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
4 | No | Azathioprine when Ig’s assayed & none for lymphocytes | 19 (5.7–12.6) | 1.1 (0.3–1.6) | 4.56 (0.8–2.3) | 4.04 X10(9)/L (1.5–7) | NA | 3.10 X10(9)/L (0.66–2.41) | 1.13 X10(9)/L (0.43–1.62) | 1.605 X10(9)/L (0.15–1.01) | 0.788 X10(9)/L (0.08–0.58) | 0.376 X10(9)/L (0.05–0.52) | 76.7 (52–78) | 28 (25–48) | 39.7 (9–35) | 19.5 (8–24) | 7.3 (4–17) |
5 | No | None | 13.3 (5.7–12.6) | 1.32 (0.3–1.6) | 4.97 (0.8–2.3) | NA | NA | 0.867 X10(9)/L (0.66–2.41) | 0.518 X10(9)/L (0.43–1.62) | 0.299 X10(9)/L (0.15–1.01) | 0.245 X10(9)/L (0.08–0.58) | 0.076 X10(9)/L (0.05–0.52) | 72.2 (52–78) | 43.2 (25–48) | 24.9 (9–35) | 20.4 (8–24) | 6.3 (4–17) |
6 | No | Post-rituximab |
4.23 (6.5–12.2) |
0.48 (0.5–2.03) | 2.38 (0.5–2.03) | 3900/μl | NA | 2769/μl (1200–1600) | 1053/μl (650–1500) | 1326/μl (370–1100) | 780/μl (270–860) | 71 (60–76) |
27 (31–47) | 34 (18–35) | 20 (13–27) | ||
7 | Yes (3 episodes of pneum-onia; dissemin-ated herpes zoster; TB reaction) | None | 20.1 (3.4–12.3) | N | N | NA | NA | NA |
0.277 X10(9)/L (0.9–2.86) |
0.384 X10(9)/L (0.63–1.91) | NA | NA | NA | NA | NA | NA | NA |
8 | Yes (2 episodes of pneum-onia) | None | 20.9 (6.7–17.3) |
0.05 (0.5–3.1) | 1.5 (0.4–3.7) | 2.7 X10(9)/L (1.5–7) | NA | NA | NA | NA | NA | NA |
32 (60–85) |
17 (30–60) |
13 (15–35) | NA | NA |
9 | No | Prednisolone, hydroxochlo-roquine & mycophenol-ate mofetil, | 19 (6.4–13.5) | 6.63 (0.7–3.1) |
0.23 (0.6–3.5) |
736/mm3 (2500–7200) |
1056/mm3 (1500–8000) |
613/mm3 (800–3500) | 421/mm3 (400–2100) |
181/mm3 (200–1200) |
26/mm3 (200–600) |
66/mm3 (70–1200) | NA | NA | NA | NA | NA |
10 | No | Prednisolone, | 17.7 (6.5–12.2) | 1.3 (0.5–2.0) |
0.23 (0.5–2.03) | NA | NA | NA | 1080/μl (650–1550) | 1800/μl (370–1100) | NA | N | NA |
27 (31–47) | 45 (18–35) | NA | NA |
11 | Yes (severe chicken-pox; skin & dental abscesses) | None | 13 (6.5–12.2) |
0.36 (0.5–2.0) | 1.56 (0.5–2.03) | 1000/μl (2500–7200) | NA |
670/μl (1200–2600) |
200/μl (650–1550) |
280/μl (370–1100) |
210/μl (270–860) |
60/μl (100–480) | 67 (60–76) |
20 (31–47) | 28 (18–35) | 21 (13–27) | 6 (4–17) |
12 | No | Steroids | 23 (6.5–12.2) | 1.9 (0.5–2.0) | 1.1 (0.5–2.03) |
1000/μl (2500–7200) | NA | NA |
300/μl (700–2200) |
420/μl (490–1300) |
80/μl (390–1400) | NA | NA | NA | NA | NA | NA |
13 | No | None | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
14 | No | Prednisolone | 13 (6.5–14.5) | 1.56 (0.5–2) | 2.09 (0.45–2.5) | 3.9 X10(9)/L (0.8–5) | 3.49 X10(9)/L (1.6–7) | NA | NA | NA | NA | NA | 77 | 35 | 38 | 11 | |
15 | No | Prednisolone & azathioprine | 15.8 (6–16) | 0.95 (0.3–1.9) | 2.84 (0.4–3.75) | NA | NA | 1084/μl (800–3500) | 727/μl (400–2100) | 333/μl (200–1200) |
131/μl (200–600) |
13/μl (70–1200) | 89 (52–78) | 60 (25–48) | 27 (9–35) | 11 (8–24) |
1 (6–27) |
16 | No | Prednisolone | 38.8 (5.5–16.3) | 0.6 (0.6–2.9) | 1.75 (0.8–4.5) | 2700/mm3 (2500–7200) | 2200/mm3 (1500–8000) | NA | NA | NA | NA | NA | 80.6 (57–86) | 29.3 (29–57) | 45.8 (13–47) | 11.75 (3.5–15.5) | 5.75 (4.5–30) |
17 | No | Prednisolone | NA | 1.1 (0.6–2.9) | 3.84 (0.8–4.5) |
1600/mm3 (2500–7200) | 3000/mm3 (1500–8000) | NA | NA | NA | NA | NA | 63 (57–86) |
25.6 (29–57) | 33.4 (13–47) | 27.5 (3.5–15.5) |
4 (4.5–30) |
19 | Yes | Azathioprine | 17 (6.2–14.4) | 0.77 (0.5–2.6) | 1.67 (0.7–2.9) | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
20 | No | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
21 | Yes (frequent RTI <1 yr.) | Prednisolone | NA | NA | NA |
1550/mm3 (2500–7200) | 7660//mm3 (1500–8000) | NA | NA | NA | NA | NA |
16.8 (57–86) |
4 (29–57) |
12 (13–47) | 74.3 (3.5–15.5) | 8.5 (4.5–30) |
22 | No | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
23 | No | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
24 | No | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
25 | No | None | 12.1 (5–13) | 0.8 (0.5–1.6) | 1.2 (0.4–1.7) | NA | NA | 3.13 X10(9)/L (0.66–2.41) | 1.23 X10(9)/L (0.43–1.62) | 1.82 X10(9)/L (0.15–1.01) | 0.59 X10(9)/L (0.08–0.58) | 0.2 X10(9)/L (0.05–0.52) | 79 | 31 | 46 | 15 | 5 |
26 | No | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
Total | 5/25 (1 NA) | ||||||||||||||||
1/15 |
Causes of Death and Severe Disability
Discussion
Patient (Pt.) | Gender | Consanguinity (relationship to other patients) | SPENCD skeletal dysplasia | Short stature (standard Deviation (SD) below the mean) | Neurological disease | Intracranial calcification | Immune phenotype |
---|---|---|---|---|---|---|---|
Schorr et al. [1] Pt. 1 | Male | Yes (sibling of Pt. 2 [1]) | Yes | Yes | No | NR | NR |
Schorr et al. [1] Pt. 2 | Male | Yes (sibling of Pt. 1 [1]) | Yes | Yes | No | NR | NR |
Gustavson et al. [21] Pt. 1 | Female | No (sibling of Pt. 2 [21]) | Yes | Yes (−7.5SD at 16 years) | No | NR | NR |
Gustavson et al. [21] Pt. 2 | Male | No (sibling of Pt. 1 [21]) | Yes | Yes (−6.5SD at 13 years) | No | NR | NR |
Spranger et al. [22] Pt. 1 | Male | No | Possibly1
| Yes | No | NR | NR |
Spranger et al. [22] Pt. 2 | Male | NR | Possibly2
| Yes | Dev. delay | NR | NR |
Spranger et al. [22] Pt. 3 | Male | No | Possibly3
| Yes | Dev. delay | NR | NR |
Sauvegrain et al. [23] Pt. 1 | Female | No | Yes | Yes | No | NR | NR |
Sauvegrain et al. [23] Pt. 5 | Male | Yes | Yes | Yes | Dev. delay | NR | NR |
Chagnon et al. [24] | Male | No | Yes | Yes | Spasticity | NR | NR |
Azouz [25] | Male | No | Yes | Yes | No | NR | NR |
Ziv et al. [31] Pt. 1 | Male | No (sibling of Pt. 2 [31]) | Yes | Yes | NR | NR | NR |
Ziv et al. [31] Pt. 2 | Female | No (sibling of Pt. 1 [31]) | Yes | Yes | NR | NR | NR |
Menger et al. [30] Pt. 1 | Male | Yes (sibling of Pt. 2 [30]) | Yes | Yes (−6SD at 12 years) | Dev. delay | NR | NR |
Menger et al. [30] Pt. 2 | Male | Yes (sibling of Pt. 1 [30]) | Yes | Yes (−6SD at 6 years) | Dev. delay | NR | NR |
Menger et al. [30] Pt. 3 | Male | Yes (distant relative of Pt. 1 and 2 [30]) | Yes | Yes (−1.5SD at 12 years) | No | NR | NR |
Menger et al. [30] Pt. 4 | Male | Yes | Yes | Yes (−2SD at 6 years) | Dev. delay & spasticity | NR | NR |
Frydman et al. [4] Pt. 1 | Male | Yes (sibling of Pt. 18 in present cohort) | Yes | Yes (−3.5SD at 8 years) | No | No | No |
Frydman et al. [4] Pt. 3 | Male | Yes | Yes | NR | NR | NR | NR |
Frydman et al. [4] Pt. 5 | Male | Yes (sibling of Pt. 22 in present cohort) | Yes | Yes (−4.4SD at 8 years) | Dev. delay & spasticity | Yes | No |
Frydman et al. [4] Pt. 6 | Male | No | Yes | Yes (−5.4SD at 8 years) | No | Yes | NR |
Robinson et al. [28] Pt. 1 | Male | No (grandson of Pt. 2 [28]) | Yes | Yes (−3SD at 19 years) | No | NR | NR |
Robinson et al. [28] Pt. 2 | Male | NR (paternal grandfather of Pt. 1 [28]) | Yes | Yes (−5.5SD at 86 years) | NR | NR | NR |
Passwell et al. [32] Pt. 1 | Male | Yes (sibling with skeletal phenotype, data limited) | Yes | Yes | NR | Yes | SLE |
Passwell et al. [32] Pt. 2 | Female | Yes (sibling with skeletal phenotype, data limited) | Yes | Yes | NR | NR | SLE |
Passwell et al. [30] Pt. 3 | Female | Yes | Yes | Yes | NR | NR | SLE |
Uhlmann et al. [26] Pt. 1 | Male | No | Yes | Yes (−4SD at 5 years) | No | NR | NR |
Uhlmann et al. [26] Pt. 2 | Male | No | Yes | Yes | NR | NR | NR |
Tuysuz et al. [5] Pt. 1 | Male | No (sibling of Pt. 2 [5]) | Yes | Yes (−4.5SD at 9 years) | No | No | NR |
Tuysuz et al. [5] Pt. 2 | Female | No (sibling of Pt. 1 [5]) | Yes | Yes (−1.5SD at 21 years)4
| No | No | NR |
Tuysuz et al. [5] Pt. 3 | Male | NR | Yes | Yes (−4.5SD at 7 years) | Dev. delay | Yes | NR |
Bhargava et al. [29] Pt. 1 | Male | No (son of Pt. 2 [29]) | Yes | Yes (−2.5SD at 13 years) | No | NR | NR |
Bhargava et al. [29] Pt. 2 | Female | No (mother of Pt. 1 [29]) | Yes | Yes (−2.5SD at 42 years) | No | NR | NR |