An Illustrative Case Of Léri-weill Dyschondrosteosis

We report on a girl presenting Léri-Weill dyschondrosteosis (LWD) due to deletion of the SHOX gene. Her family included individuals with short stature alone or with both short stature and mesomelia or Madelung's deformity. The deletion was demonstrated through detection of hemizygosity for microsatellite markdrs SHOX-CA repeat, DXYS10092, DXYS10093 and DXYS10091 localized around the SHOX gene, with retention of paternal alleles in the proband and three of her sisters who had short stature as the only clinical feature. Hemizygosity for these loci was also observed in their mother, who had short stature too. The deletion in the proband was however larger, including locus DXY 10083. The proband's only sister with normal height did not carry the deletion. Family history suggests transmission of the deletion from the proband's maternal great-grandfather to her grandfather via the Y chromosome, and from the grandfather to the proband's mother via the X chromosome after crossing-over in the pseudoautosomal region proximal to the SHOX gene. Copyright © 2008, Sociedade Brasileira de Genética.314839842Belin, V., Cusin, V., Viot, G., Girlich, D., Toutain, A., Moncla, A., Vekemans, M., Cormier-Daire, V., SHOX mutations in dyschondrosteosis (Léri-Weill syndrome) (1998) Nat Genet, 19, pp. 67-69Benito-Sanz, S., del Blanco, D.G., Aza-Carmona, M., Magano, L.F., Lapunzina, P., Argente, J., Campos-Barros, A., Heath, K.E., PAR1 deletions downstream of SHOX are the most frequent defect in a Spanish cohort of Léri-Weill dyschondrosteosis (LWD) probands (2006) Hum Mutat, 27, p. 1062Benito-Sanz, S., del Blanco, D.G., Huber, C., Thomas, N.S., Aza-Carmona, M., Bunyan, B., Maloney, V., Campos-Barros, A., Characterization of SHOX deletions in Léri-Weill dyschondrosteosis (LWD) reveals genetic heterogeneity and no recombination hotspots (2006) Am J Hum Genet, 79, pp. 409-412Benito-Sanz, S., Thomas, N.S., Huber, C., Gorbenko del Blanco, D., Aza-Carmona, M., Crolla, J.A., Maloney, V., Campos-Barros, A., A novel class of pseudoautosomal region 1 deletions downstream of SHOX Is associated with Léri-Weill dyschondrosteosis (2005) Am J Hum Genet, 77, pp. 533-544Clement-Jones, M., Schiller, S., Rao, E., Blaschke, R.J., Zuniga, A., Zeller, R., Robson, S.C., Strachan, T., The short stature homeobox gene SHOX is involved in skeletal abnormalities in Turner syndrome (2000) Hum Mol Genet, 9, pp. 695-702Ellison, J.W., Wardak, Z., Young, M.F., Gehron Robey, P., Laig-Webster, M., Chiong, W., PHOG, a candidate gene for involvement in the short stature of Turner syndrome (1997) Hum Mol Genet, 6, pp. 1341-1347Filatov, D.A., Gerrard, D.T., High mutation rates in human and ape pseudoautosomal genes (2003) Gene, 317, pp. 67-77Fukami, M., Kato, F., Tajima, T., Yokoya, S., Ogata, T., Transactivation function of an approximately 800-bp evolutionarily conserved sequence at the SHOX 3′ region: Implication for the downstream enhancer (2006) Am J Hum Genet, 78, pp. 167-170Henry, A., Thorburn, M.J., Madelung's deformity. A clinical and cytogenetic study (1967) J Bone Joint Surg, 49 B, pp. 66-73Jorge, A.A., Souza, S.C., Nishi, M.Y., Billerbeck, A.E., Liborio, D.C., Kim, C.A., Arnhold, I.J., Mendonca, B.B., SHOX mutations in idiopathic short stature and Leri-Weill dyschondrosteosis: Frequency and phenotypic variability (2007) Clin Endocrinol, 66, pp. 130-135Lien, S., Szyda, J., Schechinger, B., Rappold, G., Arnheim, N., Evidence for heterogeneity in recombination in the human pseudoautosomal region: High resolution analysis by sperm typing and radiation-hybrid mapping (2000) Am J Hum Genet, 66, pp. 557-566Rao, E., Weiss, B., Fukami, M., Rump, A., Niesler, B., Mertz, A., Muroya, K., Winkelmann, M., Pseudoautosomal deletions encompassing a novel homeobox gene cause growth failure in idiopathic short stature and Turner syndrome (1997) Nat Genet, 16, pp. 54-63Rappold, G., Blum, W.F., Shavrikova, E.P., Crowe, B.J., Roeth, R., Quigley, C.A., Ross, J.L., Niesler, B., Genotypes and phenotypes in children with short stature: Clinical indicators of SHOX haploinsufficiency (2007) J Med Genet, 44, pp. 306-313Rappold, G.A., Fukami, M., Niesler, B., Schiller, S., Zumkeller, W., Bettendorf, M., Heinrich, U., Onigata, K., Deletions of the homeobox gene SHOX(short stature homeobox) are an important cause of growth failure in children with short stature (2002) J Clin Endocrinol Metab, 87, pp. 1402-1406Schneider, K.U., Sabherwal, N., Jantz, K., Röth, R., Muncke, N., Blum, W.F., Cutler Jr, G.B., Rappold, G., Identification of major raombinant hotspot in patients with short stature and SHOX deficiency (2005) Am J Hum Genet, 77, pp. 89-96Shears, D.J., Vassal, H.J., Goodman, F.R., Palmer, R.W., Reardon, W., Superti-Furga, A., Scambler, P.J., Winter, R.M., Mutation and deletion of the pseudoautosomal gene SHOX cause Léri-Weill dyschondrosteosis (1998) Nat Genet, 19, pp. 70-72Zebala, L.P., Manske, P.R., Goldfarb, C.A., (200't) Madelung's deformity: A spectrum of presentation.. The J Hand Surg, 32 A, pp. 1393-1401Zinn, A.R., Ramos, P., Ross, J., (1006) A second recombination hotspot associated with SHOX deletions Am J Hum Genet, 78, pp. 523-52

In silico before in vivo: How to predict the heating efficiency of magnetic nanoparticles within the intracellular space

This work aims to demonstrate the need for in silico design via numerical simulation to produce optimal Fe 3 O 4 -based magnetic nanoparticles (MNPs) for magnetic hyperthermia by minimizing the impact of intracellular environments on heating efficiency. By including the relevant magnetic parameters, such as magnetic anisotropy and dipolar interactions, into a numerical model, the heating efficiency of as prepared colloids was preserved in the intracellular environment, providing the largest in vitro specific power absorption (SPA) values yet reported. Dipolar interactions due to intracellular agglomeration, which are included in the simulated SPA, were found to be the main cause of changes in the magnetic relaxation dynamics of MNPs under in vitro conditions. These results pave the way for the magnetism-based design of MNPs that can retain their heating efficiency in vivo, thereby improving the outcome of clinical hyperthermia experiments

Low dose Naltrexone for induction of remission in inflammatory bowel disease patients

Background: Around 30% of patients with inflammatory bowel disease (IBD) are refractory to current IBD drugs or relapse over time. Novel treatments are called for, and low dose Naltrexone (LDN) may provide a safe, easily accessible alternative treatment option for these patients. We investigated the potential of LDN to induce clinical response in therapy refractory IBD patients, and investigated its direct effects on epithelial barrier function. Methods: Patients not in remission and not responding to conventional therapy were offered to initiate LDN as a concomitant treatment. In total 47 IBD patients prescribed LDN were followed prospectively for 12 weeks. Where available, endoscopic remission data, serum and biopsies were collected. Further the effect of Naltrexone on wound healing (scratch assay), cytokine production and endoplasmic reticulum (ER) stress (GRP78 and CHOP western blot analysis, immunohistochemistry) were investigated in HCT116 and CACO2 intestinal epithelial cells, human IBD intestinal organoids and patient samples. Results: Low dose Naltrexone induce

Translation and validation of the Brazilian version of the Cerebral Palsy Quality of Life Questionnaire for Children – child report

AbstractObjectiveTo verify the psychometric properties of the Cerebral Palsy: Quality of Life Questionnaire Children – child report (CPQol-Child) questionnaire, after it was translated and culturally adapted into Brazilian Portuguese.MethodsAfter the translation and cultural adaptation of the tool into Brazilian Portuguese, the questionnaire was answered by 65 children with cerebral palsy, aged 9–12 years. The intraclass correlation coefficient and Cronbach's alpha were used to assess the reliability and internal consistency of the tool and its validity was analyzed through the association between CPQol-Child: self-report tool and Kidscreen-10 using Pearson's correlation coefficient.ResultsInternal consistency ranged from 0.6579 to 0.8861, the intraobserver reliability from 0.405 to 0.894, and the interobserver from 0.537 to 0.937. There was a weak correlation between the participation domain and physical health of CPQol-Child: self-report tool and Kidscreen-10.ConclusionThe analysis suggests that the tool has psychometric acceptability for the Brazilian population

Feeding strategies and energy to protein ratio on tambaqui performance and physiology

The objective of this work was to evaluate the effect of feed deprivation and refeeding with diets containing different energy to protein ratios (E/P) on the performance and physiology of juvenile tambaqui (Colossoma macropomum). A 4x2 factorial arrangement with three replicates was used, with four E/P ratios (11.5, 10.5, 9.5, and 8.5 kcal g-1 digestible energy per protein) and two feeding regimens (with and without deprivation), during 60 days. Fish from the food-deprived group were fasted for 14 days and refed from the fifteenth to the sixtieth day, whereas the remaining fish were fed for 60 days. At the end of the experimental period, weight of fish subjected to food deprivation was lower than that of those continuously fed; however, this condition did not influence the physiological parameters analyzed. Tambaqui fed 11.5 kcal g-1 achieved lower final weight than those fed with the other diets, in both regimens. Among the physiological parameters, only plasma protein presented significant increase in fish fed 8.5 kcal g-1, in both feeding regimens, probably due to the higher dietary protein concentration. These results indicate that fish show a partial compensatory growth, and that 10.5 kcal g-1 can be recommended for the diet of juvenile tambaqui