Bone marrow plasma macrophage inflammatory protein protein-1 alpha(MIP-1 alpha) and sclerostin in multiple myeloma: relationship with bone disease and clinical characteristics.

The aim of the study was to investigate the expression of MIP-1 alpha and sclerostin in bone marrow of patients with multiple myeloma (MM), the possible association of the sclerostin and MIP-1 alpha with MBD and the clinical characteristics. 53 patients (29 M, 24 F), median age 64 years was studied. MIP-1 alpha, sclerostin and bone-specific alkaline phosphatase (bALP) levels were quantified using an enzyme-linked immunosorbent assay (ELISA). Sclerostin and MIP-1 alpha mRNA expression was determined by RT-PCR. PTH and 1,25(OH) 2D3 levels were measured with an electrochemiluminescence immunoassay. The sclerostin and MIP-1 alpha concentrations in patients with MM were higher than those in the controls. RT-PCR analysis verified that the bone marrow mononuclear cells (BMMNCs) of most patients showed sclerostin and MIP-1 alpha mRNA expression. The sclerostin and MIP-1 alpha levels in patients with ISS stage III disease were significantly higher than those in patients with ISS stage II disease (p=0.01 and 0.06). The sclerostin and MIP-1 alpha levels in patients with BMD in group C were significantly higher than those in group A+B. There was positive correlation between sclerostin levels and MIP-1 alpha, beta2-microglobulin and aCa levels. A negative association was seen between sclerostin levels and bALP, HB and ALB levels. The MM patients with high sclerostin levels (>0.72 ng/ml) had significantly shorter median survival than those with low sclerostin levels (≤0.72 ng/ml) (χ(2)=7.574, p=0.006). Our findings support the positive relationship between sclerostin levels and MIP-1alpha levels deserve further detailed research.

[A new mutation in the GJB1 gene of a Chinese family with Charcot-Marie-Tooth disease associated with vocal cord paresis].

OBJECTIVE: To report an X-linked dominant Charcot-Marie-Tooth disease (CMTX) Chinese family with vocal cord paresis and to identify the mutation of gap junction protein beta 1 gene (GJB1). METHODS: Part of the family members with dysphagia, dysphonia and lethal respiratory failure were studied through flexible laryngoscope, clinical, brain MRI and electrophysiological examinations. After excluding large fragment tandem duplication containing peripheral myelin protein 22 gene (PMP22), direct sequencing was performed to analyze the mutation of the GJB1 gene in 5 patients including the proband, 5 unaffected family members and 50 unrelated healthy individuals. RESULTS: Eight members spanning 3 generations in this family were affected with CMTX characterized by progressive atrophy and weakness of the anterior tibial and peroneal muscles, especially in the proband. Vocal cord paresis was observed through flexible laryngoscope in total of 4 affected members with dysarthria and dysphagia, 2 of them died of severe respiratory failure due to complete bilateral vocal cord involvement. Normal brain MRI was observed in the proband. The electrophysiological data showed predominant demyelization involving the motor and sensory nerves in the proband. DNA sequencing revealed a de novo c.186 C>G missense mutation in exon 2 of the GJB1 gene, the mutation cosegregated with phenotype. CONCLUSION: Respiratory failure associated with vocal cord involvement may be a rare and severe symptom in CMTX. The present report provides further evidence for clinical and genetic heterogeneity in the X-linked Charcot-Marie-Tooth disease.