Fig. 1Radiographic signatures of the patient with type II autosomal dominant osteopetrosis. (A) Mile sclerosis of skull base and cortical thickening (arrowhead). (B) Cortical thickening (arrowheads) in femurs. LAT-LT, lateral-left.
Fig. 2Bone mineral density (BMD), T and Z score in the patient with type II autosomal dominant osteopetrosis. (A) BMD at lumbar spine. (B) BMD at left femur. The reference data for the Z score was calculated from healthy Asian people of the same age and sex. BMC, bone mineral content.
Fig. 3Whole-body bone scintigraphy with technetium 99m-methyl diphosphonate. Tracer uptake in proximal epiphysis of both the humeri, tibias and fibulas, head and acetabulum of the femurs was increased. Faint visualization of both kidneys and bladder. RT, right; IV, intravenous; ANT, anterior; POST, posterior.
Fig. 4Genetic analysis of chloride voltage-gated channel 7 (CLCN7) gene in the patient with type II autosomal dominant osteopetrosis (ADO II). Direct DNA sequencing of the patients with ADO II; arrow indicates a heterozygous A-to-G transition at c.296 in exon 4, leading to p.Tyr99Cys.
Fig. 5Alignment of the product of chloride voltage-gated channel 7 (CLCN7) indicating the conservation of mutated residues (Y99C) among different species.
Fig. 6Polymorphism Phenotyping v2 (PolyPhen-2) can predict the possible impact of amino acid substitutions on the stability and function of human proteins using structural and comparative evolutionary considerations. The missense mutations Y99C in chloride voltage-gated channel 7 (CLCN7) were predicted to have a pathogenic effect.
Table 1Laboratory Findings of the Patient with ADO II
Laboratory findings |
Value |
Hemoglobin, g/dL |
13.4 |
White blood cells, k/μL |
5.24 |
Platelet, k/μL |
225 |
Blood urea nitrogen, mg/dL |
15.0 |
Creatinine, mg/dL |
0.42 |
Na/K, mEq/L |
139.9/4.0 |
Total protein, g/dL |
6.4 |
Albumin, g/dL |
4.0 |
Calcium/phosphorus, mg/dL |
8.6/4.7 |
Alkaline phosphatase, IU/L |
59 |
C-telopeptide, ng/mL |
0.349 |
Bilirubin, mg/dL |
0.82 |
Aspartate transaminase/alanine transaminase, IU/L |
38/15 |
Parathyroid hormone, mIU/mL |
29.37 |
25-Hydroxy vitamin D, ng/mL |
16.3 |
Free T4, ng/dL |
0.99 |
T3, ng/mL |
1.32 |
Thyroid stimulating hormone, μIU/mL |
2.54 |
24-Hour urine creatinine, g/day |
0.73 |
24-Hour urine phosphorus, mg/day |
628.25 |
24-Hour urine calcium, mg/day |
288.75 |
24-Hour urine sodium, mEq/day |
112.7 |