Fibrodysplasia Ossificans Progressiva with Rare Familial Inheritance Pattern: A Case Series.

Fibrodysplasia ossificans progressive (FOP)also termed as “stone man syndrome” is an autosomal dominant disorder manifested in the form of congenital malformation of the great toes with progressive ossification of the skeletal muscle and soft tissues in a specific pattern. It is a rare disorder, usually as sporadic and isolated and very few cases have been reported. Often FOP is missed or diagnosed very late, both of which leads to rapid progression and reduced life expectancy. We report first of such a case series in India with the hereditary transmission in a family, affecting 3 persons. Our index case was the first daughter 17 years female who presented with stiff joints, worsening over time and her father 45 years male was also affected with his major joints fused in different positions, and her younger sister 13 years female was in the early stage of disease. Further investigations such as serum calcium, phosphorous, X-ray, computed tomography, and bone scan confirmed it as cases of FOP. We present our detailed study of the interventions, their effectiveness, the role of drugs given to reduce symptoms in FOP, and this would aid the physicians and healthcare workers to suspect/diagnose the disease.

Point Mutation of Hoxd12 in Mice

PURPOSE: Genes of the HoxD cluster play a major role in vertebrate limb development, and changes that modify the Hoxd12 locus affect other genes also, suggesting that HoxD function is coordinated by a control mechanism involving multiple genes during limb morphogenesis. In this study, mutant phenotypes were produced by treatment of mice with a chemical mutagen, N-ethyl-N-nitrosourea (ENU). We analyzed mutant mice exhibiting the specific microdactyly phenotype and examined the genes affected. MATERIALS AND METHODS: We focused on phenotype characteristics including size, bone formation, and digit morphology of ENU-induced microdactyly mice. The expressions of several molecules were analyzed by genome-wide screening and quantitative real-time PCR to define the affected genes. RESULTS: We report on limb phenotypes of an ENU-induced A-to-C mutation in the Hoxd12 gene, resulting in alanine-to-serine conversion. Microdactyly mice exhibited growth defects in the zeugopod and autopod, shortening of digits, a missing tip of digit I, limb growth affected, and dramatic increases in the expressions of Fgf4 and Lmx1b. However, the expression level of Shh was not changed in Hoxd12 point mutated mice. CONCLUSION: These results suggest that point mutation rather than the entire deletion of Hoxd12, such as in knockout and transgenic mice, causes the abnormal limb phenotype in microdactyly mice. The precise nature of the spectrum of differences requires further investigation.