Split-hand/feet malformation in three tamilian families and review of the reports from India

Split-hand/foot malformation (SHFM) is a rare condition which can be either syndromic or nonsyndromic. We report three unrelated pedigrees, one with autosomal dominant (AD) inheritance and the other two with autosomal recessive (AR) pattern. We also briefly review the published reports from India.     

Zinc supplementation to protein-deficient diet in CO-exposed mice decreased fetal mortality and malformtion

In developing countries, diet during pregnancy is frequently low in both protein and zinc contents and exposure to CO is common because of environmental pollution and smoking. This study was conducted to evaluate whether zinc supplementation ameliorates fetal mortality and malformations in protein-deficient, CO-exposed mice. Pregnant mice of the CD-1 strain were maintained on 17% (reference) or 9% protein diets mixed with deficient, normal, or supplemental zinc throughout gestation. The dams in each dietary group were exposed to air (control) or 500 ppm CO in air in environmental chambers from gestation days 7–18. As compared to the control group (normal protein, normal zinc), the incidence of fetal mortality was 66.8% and 57.2% higher, respectively, and malformation incidence was 74.4% and 72.4% higher (0 and 500 ppm CO, respectively) in mice fed both deficient protein-zinc diets. However, the highest malformation rate was observed in the group with normal protein, deficient zinc (96% mortality in both 500 and 0 ppm CO, as compared to the reference group, p<0.0001). The fetal mortality rate was −3.5% (0 ppm CO) and 25.4% (500 ppm CO) lower in zinc-supplemented, protein-deficient groups compared to the control group. There was a significant negative association between fetal zinc concentrations and fetal malformations (p≤0.001). The result of this study might be relevant to populations that are exposed to CO and or consume marginal zinc and protein diets during gestation.     

Interactive effects of cadmium and all-trans-retinoic acid on the induction of forelimb ectrodactyly in C57BL/6 mice

BACKGROUND: Most toxicological studies have tested single chemical agents at relatively high doses, and fewer studies have addressed the toxic effects of chemical interactions. It is important to understand the toxicity of chemical mixtures in order to assess the more realistic risks of environmental and occupational exposures. A number of chemicals are known to induce a predominantly postaxial forelimb ectrodactyly in C57BL/6 mice, including acetazolamide, ethanol, cadmium, valproic acid, carbon dioxide, dimethadione, phenytoin, and 13-cis-retinoic acid and all-trans-retinoic acid (RA). In the present study, the interactive effects of coadministration of cadmium and RA on developing limbs were investigated. METHODS: Pregnant C57BL/6 mice were treated with different intraperitoneal (IP) doses of cadmium chloride (CdCl2) and/or RA on gestational day (GD) 9.5, and fetuses were collected on GD 18 and double stained for examination of skeletal defects. RESULTS: When RA was given simultaneously with cadmium, a significant increase in the incidence and severity of forelimb ectrodactyly (predominantly postaxial) was observed compared to the results with corresponding doses of cadmium or RA alone. When mice were exposed to subthreshold doses of both cadmium (0.5 mg/kg) and RA (1 mg/kg), the combined treatment exceeded the threshold, resulting in forelimb ectrodactyly in 19% of the fetuses. Moreover, coadministration of cadmium and RA at doses exceeding the respective thresholds showed a synergistic effect, that is, 92% of fetuses were found with the forelimb defect as opposed to 10% if the response were additive. CONCLUSIONS: The findings demonstrate that concurrent exposure to these teratogens can have a synergistic effect and that subteratogenic doses may combine to exceed a threshold.     

HoxD-13在先天性肛门直肠畸形患儿末端直肠组织中的表达意义及与切口感染的关系

摘要 目的：探讨HoxD-13在先天性肛门直肠畸形（CAM）患儿末端直肠组织中的基因表达意义及与术后切口感染的关系。方法：选择2015年6月-2019年06月CAM患儿71例作为观察组,选择非CAM患儿12例作为对照组。采用实时荧光PCR（RT-PCR）检测两组直肠末端组织Hoxd-13基因表达情况;记录观察组性别、年龄、体重、CAM临床分型、其它系统合并畸形情况、手术方式、成形次数、是否发生术后切口感染等,分析上述不同情况下HoxD-13基因表达水平的差异;采用线性回归分析CAM临床分型与合并其它畸形情况、HoxD-13基因表达水平的关系;观察术后切口感染相关因素,采用单因素分析、二元Logistic分析探索切口感染的危险因素。结果：观察组CAM患儿末端直肠组织中HoxD-13相对表达量低于对照组,差异有统计学意义（P<0.05）。合并其它畸形患儿的HoxD-13相对表达量低于未合并患儿,差异具有统计学意义（P<0.05）。中高位CAM患儿合并其它畸形患病率72.09%,高于低位CAM患儿（21.43%）,差异具有统计学意义（P<0.05）;中高位CAM患儿的HoxD-13相对表达量低于低位CAM,差异具有统计学意义（P<0.05）;线性回归提示HoxD-13相对表达量是影响临床分型的主要因素（t=4.714,P=0.000）。切口感染单因素分析提示,发生术后切口感染的CAM患儿的临床分型、合并其他畸形情况及直肠末端组织HoxD-13相对表达量与未发生切口感染患儿相比,存在统计学差异（P＜0.05）;二元Logistic分析结果表明,HoxD-13是术后切口感染的危险因素（Wald χ²值=7.440,P=0.006）。结论：HoxD-13基因在CAM患儿末端直肠组织中呈低表达,可能是CAM临床分型及合并其它畸形的主要因素,且可能是术后切口感染的危险因素,因此对胎儿或患儿Hoxd-13基因表达情况进行检测有一定的临床价值。     

Defence-related biochemical changes by elicitor of malformation pathogen,Fusarium mangiferae,in mango

Malformation of mango (Mangifera indica L.) induced by Fusarium moniliforme var. subglutinans is a plant disease of international importance. The paper reports the downstream defence responses at the initial stage in a susceptible host (cultivar Amrapali) after treatment with biotic (isolated from the pathogen cell wall) (BEL) and abiotic (salicylic acid, SA) elicitors, and inoculation of vegetative buds with the pathogen (IVB). The SA was further tested to induce resistance in field trials. The inoculation and application of elicitors increased β-1, 3 glucanase that causes lysis of fungal hyphae by many folds. Hydrogen peroxide (H₂O₂) (active oxygen species) that induces hypersensitive cell death was reduced to the minimum level after treatment with BEL. The reduction of H₂O₂ in the inoculated vegetative buds was also substantial; however, comparatively less with SA treatment. Consequently, there was no hypersensitive cell death in the malformed mango. Salicylic acid that enhances H₂O₂ content by suppressing H₂O₂-degradation by catalase, increased marginally with the SA treatment and in the IVB, but reduced with the BEL. The reduction of SA in BEL-treated buds concomitantly reduced its H₂O₂ content. The activity of catalase, suppressor of resistance mechanism, was reduced in all the treatments, but the reduction was not enough to arrest H₂O₂-degradation. Magiferin (1, 3, 6, 7-tetrahdroxyxanthone C₂-β-D glucoside), a defence metabolite of mango, increased substantially in all the treatments; maximum with the BEL. A pathogenesis-related (PR) protein of 20 KDa that resists symptom development appeared in all the treatments except the control. But light colour of the spots for the PR-protein indicated low protein accumulation. The maximum accumulation was with the IVB followed by SA and BEL treatments. The amount of total protein reduced considerably in all the treatments. The SA treatment on healthy plants failed to induce defence against malformation. Contrarily, the treatment on malformed seedlings restored normal growth within two months. Hence, SA acted better over the infected plants in presence of the pathogen. Thus, a signal transduction system involving SA and H₂O₂ remained nonfunctional and enough defence chemicals could not be synthesised. Defence genes that produce phenolic and β-1, 3 glucanase, however, became activated and saved the plants from death although could not prevent symptom manifestations.     

Biocontrol potential of Trichoderma species against mango malformation pathogens

Malformation disease of Mango (Mangifera indica L.) caused by Fusarium moniliforme var. subglutinans is one of the most destructive diseases, which is a major production constraint in the mango-growing regions of India. In this study, The bioagents Trichoderma viride (Tr1), Trichoderma virens (Tr2) and Trichoderma harzianum (Tr3) were evaluated in culture with the pathogens to monitor the antagonistic effect and their volatile compound and culture filtrates (non-volatile compound). It was found that all the three isolates of bioagents significantly checked the growth of F. moniliforme var. subglutinans. In dual culture, the best result was obtained with T. harzianum followed by T. virens and T. viride. A similar result was also observed in the case of culture filtrates ofTrichoderma spp. The results clearly showed that inhibition of the growth of the fusaria isolates by T. harzianum was significantly superior to T. viride andT.virens. In case of antifungal activity of volatile compounds released by Trichoderma isolates, it was also observed that T. virens was more superior to T.harzianum and T. viride.     

De novo 3q22.1 q24 deletion associated with multiple congenital anomalies,growth retardation and intellectual disability

We describe a boy with a de novo deletion of 15.67 Mb spanning 3q22.1q24. He has bilateral micropthalmia, ptosis, cleft palate, global developmental delay and brain, skeletal and cardiac abnormalities. In addition, he has bilateral inguinal hernia and his right kidney is absent. We compare his phenotype with seven other patients with overlapping and molecularly defined interstitial 3q deletions. This patient has some phenotypic features that are not shared by the other patients. More cases with smaller deletions defined by high resolution aCGH will enable better genotype–phenotype correlations and prioritizing of candidate genes for the identification of pathways and disease mechanisms.