Familial tumoral calcinosis in two Chinese patients: a case series

Abstract Introduction Tumoral calcinosis is a rare and benign condition characterized by massive subcutaneous soft tissue deposits of calcium phosphate predominantly around large joints. Case presentation Familial tumoral calcinosis was present in two members of a Han Chinese family, namely, the son and daughter. The 14-year-old son had the first operation on his right sole of the foot at the age of six, and then experienced subsequent surgeries at a lesion in his right sole of the foot and left hip, respectively. The 16-year-old daughter underwent her first operation at the age of six in her left gluteal region, and subsequent surgeries were performed due to recurrence at the same lesion. Pathologic diagnoses of surgical specimens in both of the patients were reported as tumoral calcinosis. The laboratory results showed hyperphosphatemia with normal levels of serum calcium and alkaline phosphatase. Only surgical treatment was performed in both patients with satisfactory prognosis. Conclusion This is the first report of Chinese familial tumoral calcinosis. The etiopathogenisis and treatment are discussed.</p

Newly discovered mutations in the GALNT3 gene causing autosomal recessive hyperostosis-hyperphosphatemia syndrome

Background and purpose Periosteal new bone formation and cortical hyperostosis often suggest an initial diagnosis of bone malignancy or osteomyelitis. In the present study, we investigated the cause of persistent bone hyperostosis in the offspring of two consanguineous parents

FGF-23 in bone biology

Recent studies have demonstrated that levels of fibroblast growth factor 23 (FGF-23), a key regulator of phosphorus and vitamin D metabolism, rise dramatically as renal function declines and may play a key initiating role in disordered mineral and bone metabolism in patients with chronic kidney disease (CKD). The physiologic importance of FGF-23 in mineral metabolism was first identified in human genetic and acquired rachitic diseases and further characterized in animal models. FGF-23 and its regulators, including phosphate regulating endopeptidase homolog, dentin matrix 1 (DMP1), and matrix extracellular phosphoglycoprotein, are made primarily in bone, specifically in osteocytes. Dysregulation of these proteins results in osteomalacia, implicating the osteocyte in the regulation of skeletal mineralization. Studies in pediatric patients with CKD, the majority of whom have altered skeletal mineralization in early stages of CKD, have demonstrated that skeletal expression of both FGF-23 and its regulator, DMP1, are increased in early stages of CKD and that expression of these proteins is associated with alterations in skeletal mineralization. Thus, dysregulation of osteocytic proteins occur very early in the course of CKD and appear to be central to altered bone and mineral metabolism in this patient population

Genetic diagnosis of X-linked dominant hypophosphatemic rickets in a cohort study: Tubular reabsorption of phosphate and 1,25(OH)2D serum levels are associated with PHEX mutation type

<p>Abstract</p> <p>Background</p> <p>Genetic Hypophosphatemic Rickets (HR) is a group of diseases characterized by renal phosphate wasting with inappropriately low or normal 1,25-dihydroxyvitamin D₃(1,25(OH)₂D) serum levels. The most common form of HR is X-linked dominant HR (XLHR) which is caused by inactivating mutations in the <it>PHEX </it>gene. The purpose of this study was to perform genetic diagnosis in a cohort of patients with clinical diagnosis of HR, to perform genotype-phenotype correlations of those patients and to compare our data with other HR cohort studies.</p> <p>Methods</p> <p>Forty three affected individuals from 36 non related families were analyzed. For the genetic analysis, the <it>PHEX </it>gene was sequenced in all of the patients and in 13 cases the study was complemented by mRNA sequencing and Multiple Ligation Probe Assay. For the genotype-phenotype correlation study, the clinical and biochemical phenotype of the patients was compared with the type of mutation, which was grouped into clearly deleterious or likely causative, using the Mann-Whitney and Fisher's exact test.</p> <p>Results</p> <p>Mutations in the <it>PHEX </it>gene were identified in all the patients thus confirming an XLHR. Thirty four different mutations were found distributed throughout the gene with higher density at the 3' end. The majority of the mutations were novel (69.4%), most of them resulted in a truncated PHEX protein (83.3%) and were family specific (88.9%). Tubular reabsorption of phosphate (TRP) and 1,25(OH)₂D serum levels were significantly lower in patients carrying clearly deleterious mutations than in patients carrying likely causative ones (61.39 ± 19.76 vs. 80.14 ± 8.80%, p = 0.028 and 40.93 ± 30.73 vs. 78.46 ± 36.27 pg/ml, p = 0.013).</p> <p>Conclusions</p> <p><it>PHEX </it>gene mutations were found in all the HR cases analyzed, which was in contrast with other cohort studies. Patients with clearly deleterious <it>PHEX </it>mutations had lower TRP and 1,25(OH)₂D levels suggesting that the <it>PHEX </it>type of mutation might predict the XLHR phenotype severity.</p

A gene locus responsible for the familial hair shaft abnormality pili annulati maps to chromosome 12q24.32-24.33

Pili annulati, a rare hair shaft abnormality with a characteristic shiny appearance due to alternating light and dark bands of the hair, is assumed to be inherited in an autosomal dominant mode with high penetrance. A locus for pili annulati has not been found yet. We identified one large and four small European kindreds with pili annulati and conducted a genomewide linkage analysis using 382 microsatellite markers. A multipoint logarithm of the odds (LOD) score of 3.19 was demonstrated between D12S1659 and D12S1723 on the telomeric part of the long arm of chromosome 12. Subsequent finemapping in a region of 20 cM gave a maximum multipoint LOD score of 3.24 at D12S1723 under the assumption of homogeneity and a LOD score of 3.57 around D12S343 under the assumption of heterogeneity, both exceed the statistical thresholds necessary to conclude linkage. Most of this LOD score came from the largest family, which reached a maximum LOD score of 3.81. The maximum two-point LOD score for all families was 3.97 at D12S1609. Definite recombination events narrowed the region of shared haplotype in the affected individuals to an 8 Mb region between the marker D12S324 and the telomeric end of the long arm of chromosome 12