Table 1. Clinical features and mutation spectrum of patients in our cohort.
| Subject | Patient 1 | Patient 2 | Patient 3 |
|---|---|---|---|
| Gender | Male | Male | Male |
| Age at diagnosis | 11 y | 9 y | 16 y |
| Height at diagnosis (WHO Z-score) |
125 cm (−2.75) | 122cm (−1.82) | 158 cm (−1.95) |
| Age of onset | 2 y | 4 y | 5 y |
| Joint involvement | IPJ, hip joint, elbow joint, and spine | IPJ, right knee joint, elbow joint, and spine | IPJ, hip joint and spine |
| Radiography | Hand—decreased small joint spaces with widened joints Spine—kyphoscoliosis with platyspondyly with anterior beaking Hip joint—bilateral femoral head avascular necrosis |
Hand—decreased small joint spaces with widened joints Spine—platyspondyly present |
Spine—platyspondyly present Hip joint—reduced hip joint spaces, large capital femoral epiphyses, short and broad femoral necks, and irregular acetabular roofs |
| Laboratory investigations | 25 hydroxy vitamin D: 24.67nmol/L (50–250); calcium: 8.8 mg/dL (8.5–10.8); phosphorous: 5.7 mg/dL (2.5–4.5); albumin: 4.0 gm/dL (3.5–5.5); potassium: 4.3mmol/L (3.8–5.4); creatinine: 0.7 mg/dL (0.5–1.6) | 25 hydroxy vitamin D: 38 nmol/L (50–250); calcium: 9.9mg/dL (8.5–10.8); phosphorous: 4.6 mg/dL (2.5–4.5); alkaline phosphatase: 242 IU/L Younger sibling-25 hydroxy vitamin D: 67 nmol/L (50–250); calcium: 9.1 mg/dL (8.5–10.8); alkaline phosphatase: 205 IU/L |
Hb: 8.1 gm/dL (12.5–16.5) with microcytic hypochromic anemia; TLC-12320/cu.mm (4,000–10,500); platelet: 2.11 lakh/cu.mm (1.5–4.5); potassium: 4.3 mmol/L (3.8–5.4). 25 hydroxy vitamin D: 55 nmol/L (50–250); calcium: 9.5 mg/dL (8.5–10.8) |
|
Mutation in
CCN6 (WISP3)
(Variants detected) |
1. Exon 4, homozygous variant (c.740_741del)
6
7
(p.Cys247LeufsTer31) (Sanger validated) ( Fig. S1 ) |
1. Exon 4, A heterozygous two base pair deletion (c.740_741del)
6
7
(p.Cys247LeufsTer31) 2. Exon 2, A heterozygous nonsense variation c.156C > A (p.Cys52Ter) 6 (Sanger validated) ( Fig. S2 ) |
1. Exon 4, A heterozygous single base pair duplication c.624dup (p.Cys209MetfsTer21) 8 2. Exon 4, A heterozygous 2 base pair deletion (c.740_741del) 6 7 (p.Cys247LeufsTer31) ( Fig. S3 ) |
| MAF in population databases | c.740_741del in gnomAD: 0.00000798 and 1000Genomes: absent | c.156C > A in gnomAD: 0.00003 and 1000Genomes: absent | c.624dup in gnomAD: absent and 1000Genomes: absent |
| Protein domain affected | c.740_741del: TSP | c.156C > A: IGFBP | c.624dup: TSP |
Abbreviations: Hb, hemoglobin; IGFBP, insulin-like growth factor-binding domain; IPJ, interphalangeal joint; TLC, total leucocyte count; TSP, thrombospondin domain.