A guinea-pig hereditary cataract contains a splice-site deletion in a crystallin gene

A congenital cataract present in guinea pigs provided a unique opportunity to study a hereditary lens diseases at the molecular level. ζ-crystallin, one of the most abundant guinea pig lens proteins, was found to be altered in the lens of cataractous animals. Several ζ-crystallin cDNA clones were isolated from a cataractous lens library and found to contain a 102-bp deletion towards the 3′ end of the coding region. The deletion does not interfere with the reading frame but results in a protein 34 amino acids shorter. Sequence analysis of a normal genomic ζ-crystallin clone revealed that the missing 102-bp fragment corresponds to an entire exon (exon 7). PCR analysis of the genomic DNA isolated from cataractous animals showed that exon 7, though missing from the mRNA, is intact in the cataractous genome. Further sequence analysis of the α-crystallin gene disclosed a dinucleotide delection of the universal AG at the acceptor splice-site of intron 6 of the mutant gene. The presence of this mutation results in the skipping of exon 7 during the mRNA processing which in turn results in the altered ζ-crystallin protein. This if the first time a genomic mutation in an enzyme/crytallin gene has been directly linked to a congenital cataract.     

Atrial Septal Defect in a Bonnet Macaque (Macaca radiata)

Atrial Septal Defect was detected at autopsy in a subadult bonnet macaque (Macaca radiata). Case history and autopsy findings were described.     

丙泊酚联合七氟醚麻醉在先天性心脏病介入手术患儿中的心肌保护作用及对苏醒质量和应激反应的影响

摘要 目的：研究丙泊酚联合七氟醚麻醉在先天性心脏病介入手术患儿中的心肌保护作用及对苏醒质量和应激反应的影响。方法：选择2020年1月~2022年4月期间在苏州大学附属儿童医院接受先天性心脏病介入手术患儿96例,按照双色球法将患儿分为对照组（n=48,接受瑞芬太尼、丙泊酚麻醉）和观察组（n=48,接受丙泊酚、七氟醚麻醉）。对比两组患儿心率、呼吸频率、平均动脉压、苏醒质量、心肌损伤指标、应激反应指标和不良反应发生率。结果：两组置喉罩时（T1）~拔除喉罩（T4）时间点心率、呼吸频率、平均动脉压下降后升高,观察组高于对照组同时间点（P<0.05）。观察组的苏醒时间、拔管时间均短于对照组（P<0.05）。两组术毕、术后24 h肌酸磷酸激酶同工酶（CK-MB）、心肌肌钙蛋白（cTnI）升高后下降,观察组低于对照组同时间点（P<0.05）。两组术毕、术后24 h血糖、皮质醇升高后下降,观察组低于对照组同时间点（P<0.05）。两组不良反应发生率组间对比,差异不显著（P>0.05）。结论：丙泊酚联合七氟醚麻醉应用于先天性心脏病介入手术中,可减轻患儿的应激反应,稳定机体血流动力学波动,同时还可发挥心肌保护作用,提高苏醒质量。     

Congenital defects of the upper lateral incisors (ULI): Condition and measurements of the other teeth,measurements of the superior arch,head and face

We surveyed a French male population for the incidence of missing or reduced upper lateral incisors (ULI). In 5,738 subjects, we observed an incidence of 1.59% with one or two reduced ULI (the other normal) and 1.90% with one or two missing ULI (the other normal or reduced), altogether, 3.49% affected subjects. Furthermore, 250 random controls were observed. Agenesis of other teeth is more frequent in propositi. Missing third molars were 12.4% in controls, 24.0% in propositi with reduced ULI and 39.6% in propositi with two missing ULI. Furthermore, agenesis of incisors, canines and premolars ranges from 0.4% in controls to 1.3% in propositi having reduced ULI and 5.0% in propositi with two missing ULI. So, propositi with reduced ULI are intermediate between the controls and the propositi with missing ULI with respect to the frequency of agenesis of other teeth. On the other hand, a different ranking is observed with respect to the teeth measurements: reduction of tooth size is more marked in propositi with reduced ULI than in propositi with missing ULI. The reduction mainly affects canines, incisors and to a lesser degree, premolars. Arch length and interpremolar diameters are smaller in propositi with missing ULI, compared with controls.     

Dental agenesis in the Dariusleut Hutterite Brethren: comparisons to selected Caucasoid population surveys

We report the results of a study of the prevalence of nonsyndromic dental agenesis among a sample of 208 individuals (105 females, 103 males) between the ages of 15 and 29 years from a North American religious and genetic isolate, the Dariusleut Hutterites of Western Canada. Direct examination of dental casts, oral examination reports, dental treatment records, and a limited number of dental radiographs reveals congenital absence and/or obvious morphometric reduction of at least one tooth (excluding third molars) in 98 subjects (55 females, 43 males), yielding a prevalence estimate of approximately 47%. This estimate is nearly four times those reported for nonisolate Caucasoid populations of European descent and substantially higher than the elevated prevalences observed in several other isolated populations. Although the prevalence of dental agenesis in the Dariusleut is indeed high, neither the incidence of bilateral agenesis (exhibited at least once in 58% of affected dentitions), number of affected teeth per person (mean, 2.4), morphologic tooth classes affected, or combinations of tooth classes affected ostensibly distinguish them from other populations with similar geographic origins. We conclude that the dental agenesis observed in this North American genetic isolate does not represent a private polymorphism or rare developmental variant. Consequently, the results of further study in these Dariusleut Brethren will be directly relevant to critically testing as yet unresolved hypotheses for the mode of gene action and the relative contributions of hereditary and environmental factors to the reduction of tooth numbers in human dentitions.     

喉罩通气下七氟醚全凭吸入麻醉在小儿先天性心脏病介入手术的临床麻醉效果

目的:探讨喉罩通气下七氟醚全凭吸入麻醉在小儿先天性心脏病介入手术的临床麻醉效果。方法:选取2017年4月～2019年5月期间我院收治的行先天性心脏病介入手术患儿98例,根据随机数字表法将其分为对照组(n=49)和研究组(n=49)。对照组给予氯胺酮诱导,全凭丙泊酚维持,面罩吸氧;研究组给予全凭七氟醚诱导、维持,喉罩通气。比较两组患儿麻醉前(T0)、切皮前(T1)、切皮后1 min(T2)、切皮后30 min(T3)、术后(T4)的血流动力学指标[平均动脉压(MAP)、心率(HR)]及应激反应指标[血糖、皮质醇],记录两组患儿手术时间、麻醉诱导时间、术后苏醒时间等围术期指标情况。记录两组围术期不良反应发生情况。结果:研究组手术时间、麻醉诱导时间、术后苏醒时间均短于对照组(P0.05)。两组T0时间点血糖、MAP、皮质醇、HR比较差异无统计学意义(P0.05);对照组T1～T4时间点MAP、血糖、皮质醇、HR均较T0升高(P0.05);研究组T1～T4时间点血糖、MAP、皮质醇、HR与T0时间点比较无差异(P0.05);研究组T1～T4时间点血糖、MAP、皮质醇、HR低于对照组(P0.05)。两组不良反应发生率比较无差异(P0.05)。结论:小儿先天性心脏病介入手术中应用喉罩通气下七氟醚全凭吸入麻醉,诱导迅速且安全、术后苏醒快、手术时间短,可有效维持血流动力学稳定,减少应激反应。     

Catheter ablation in children and young adults: is there an additional benefit from remote magnetic navigation?

Purpose

Although rare, children and young adults can suffer from significant cardiac arrhythmia, especially in the context of congenital malformations and after cardiac surgery.

Methods

A total of 62 patients (32 female, median age 20 years) underwent an invasive electrophysiology study between 2008–2011: half had normal cardiac anatomy, whereas the remaining patients had various types of congenital heart disease. All patients were treated using either conventional techniques (CVN) or remote magnetic navigation (RMN).

Results

Patients treated with the RMN system differed substantially from patients in the CVN group with respect to presence of congenital heart disease (67 % vs. 37 %), previous cardiac surgery (59 % vs. 20 %) or failed previous conventional ablation (22 % vs. 9 %), respectively. Although these more complex arrhythmias resulted in longer median procedure duration (180 vs. 130 min, p = 0.034), the median overall fluoroscopy exposure in the RMN group was significantly lower (4.1 vs. 5.2 min, p = 0.020). Clinical outcome was comparable in both groups without complications caused by the ablation.

Conclusions

Catheter ablation using remote magnetic navigation is safe and feasible in children and young adults and is especially valuable in patients with abnormal cardiac morphologies. RMN resulted in significantly lower radiation exposure compared with the conventional technique.     

Congenital analbuminaemia: Molecular defects and biochemical and clinical aspects

Background

DNA and mRNA sequencing of the coding regions of the human albumin gene (ALB) and of its intron/exon junctions has revealed twenty-one different molecular defects causing congenital analbuminaemia (CAA).

Scope of review

To describe the mutations in molecular terms and to present the current knowledge about the most important biochemical and clinical effects of CAA.

Major conclusions

CAA is rare, but its frequency seems to be significantly higher in restricted and minimally admixed populations. The condition affects especially the lipid metabolism but apart from a possible increased risk for atherosclerotic complications, it is generally associated with mild clinical symptoms in adults. By contrast, several reports indicate that analbuminaemic individuals may be at risk during the perinatal and childhood periods, in which they seem to show increased morbidity and mortality. The twenty-one causative defects include seven nonsense mutations, seven changes affecting splicing, five frame-shift/deletions, one frame-shift/insertion and one mutation in the start codon. These results indicate that the trait is an allelic heterogeneous disorder caused by homozygous (nineteen cases) or compound heterozygous (single case) inheritance of defects. Most mutations are unique, but one, named Kayseri, is responsible for about half of the known cases.

General significance

Study of the defects in the ALB resulting in CAA allows the identification of “hot spot” regions and contributes to understanding the molecular mechanism underlying the trait. Such studies could also give molecular information about different aspects of ALB regulation and shed light on the regulatory mechanisms involved in the synthesis of the protein. This article is part of a Special Issue entitled Serum Albumin.